CN1923171A - 同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 - Google Patents
同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 Download PDFInfo
- Publication number
- CN1923171A CN1923171A CNA2006102001714A CN200610200171A CN1923171A CN 1923171 A CN1923171 A CN 1923171A CN A2006102001714 A CNA2006102001714 A CN A2006102001714A CN 200610200171 A CN200610200171 A CN 200610200171A CN 1923171 A CN1923171 A CN 1923171A
- Authority
- CN
- China
- Prior art keywords
- methyl
- benzyloxy
- benzimidazole
- acid
- epirubicin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 35
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 title claims abstract description 10
- 239000003242 anti bacterial agent Substances 0.000 title description 8
- 229940088710 antibiotic agent Drugs 0.000 title description 8
- 239000002246 antineoplastic agent Substances 0.000 title 1
- 229940041181 antineoplastic drug Drugs 0.000 title 1
- 239000003972 antineoplastic antibiotic Substances 0.000 claims abstract description 138
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 92
- -1 Losaxantrone Chemical compound 0.000 claims abstract description 82
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 78
- 229960001904 epirubicin Drugs 0.000 claims abstract description 69
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims abstract description 60
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims abstract description 60
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 claims abstract description 48
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 claims abstract description 47
- 229960001221 pirarubicin Drugs 0.000 claims abstract description 47
- 229960004679 doxorubicin Drugs 0.000 claims abstract description 46
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 claims abstract description 45
- 229960004176 aclarubicin Drugs 0.000 claims abstract description 44
- YROQEQPFUCPDCP-UHFFFAOYSA-N losoxantrone Chemical compound OCCNCCN1N=C2C3=CC=CC(O)=C3C(=O)C3=C2C1=CC=C3NCCNCCO YROQEQPFUCPDCP-UHFFFAOYSA-N 0.000 claims abstract description 42
- 229950008745 losoxantrone Drugs 0.000 claims abstract description 42
- 239000004005 microsphere Substances 0.000 claims abstract description 32
- 229920001577 copolymer Polymers 0.000 claims abstract description 27
- 239000004626 polylactic acid Substances 0.000 claims abstract description 27
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 23
- CXMXRPHRNRROMY-UHFFFAOYSA-N n-Decanedioic acid Natural products OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 13
- 150000003230 pyrimidines Chemical class 0.000 claims abstract description 6
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims abstract description 4
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 claims abstract 3
- 239000007924 injection Substances 0.000 claims description 104
- 238000002347 injection Methods 0.000 claims description 104
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 claims description 60
- 238000013268 sustained release Methods 0.000 claims description 52
- 239000012730 sustained-release form Substances 0.000 claims description 52
- 229960000653 valrubicin Drugs 0.000 claims description 47
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 42
- 229960001156 mitoxantrone Drugs 0.000 claims description 42
- BTQAFTBKHVLPEV-UHFFFAOYSA-N 3h-naphtho[2,3-e]indazole Chemical compound C1=CC=CC2=CC3=C4C=NNC4=CC=C3C=C21 BTQAFTBKHVLPEV-UHFFFAOYSA-N 0.000 claims description 41
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 41
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- XJXLRNPVSQADMZ-UHFFFAOYSA-N n-methyl-n-[4-[(7-methyl-3h-imidazo[4,5-f]quinolin-9-yl)amino]phenyl]acetamide Chemical compound C1=CC(N(C(C)=O)C)=CC=C1NC1=CC(C)=NC2=CC=C(NC=N3)C3=C12 XJXLRNPVSQADMZ-UHFFFAOYSA-N 0.000 claims description 41
- 229950001746 piroxantrone Drugs 0.000 claims description 41
- KDRKQBMPDQDAJW-UHFFFAOYSA-N piroxantrone Chemical compound OCCNCCN1NC2=C3C(=O)C=CC(=O)C3=C(O)C3=C2C1=CC=C3NCCCN KDRKQBMPDQDAJW-UHFFFAOYSA-N 0.000 claims description 41
- 229950010138 teloxantrone Drugs 0.000 claims description 41
- QDZIHWBJFUNKOF-UHFFFAOYSA-N teloxantrone Chemical compound OCCNCCN1NC2=C3C(=O)C=CC(=O)C3=C(O)C3=C2C1=CC=C3NCCNC QDZIHWBJFUNKOF-UHFFFAOYSA-N 0.000 claims description 41
- 239000007943 implant Substances 0.000 claims description 37
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 36
- 229910019142 PO4 Inorganic materials 0.000 claims description 33
- 239000003112 inhibitor Substances 0.000 claims description 33
- 239000010452 phosphate Substances 0.000 claims description 33
- 229940060038 chlorine Drugs 0.000 claims description 31
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 30
- VGQOVCHZGQWAOI-YQRHFANHSA-N anthramycin Chemical compound N1[C@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-YQRHFANHSA-N 0.000 claims description 30
- 229950010131 puromycin Drugs 0.000 claims description 30
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 27
- 229930195573 Amycin Natural products 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 24
- 108010006654 Bleomycin Proteins 0.000 claims description 23
- 229960001561 bleomycin Drugs 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 23
- JJDMKDXGNVJWCD-UHFFFAOYSA-N 1h-benzimidazole-4-carboxamide Chemical class NC(=O)C1=CC=CC2=C1N=CN2 JJDMKDXGNVJWCD-UHFFFAOYSA-N 0.000 claims description 22
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical class CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 claims description 22
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 21
- SEKJSSBJKFLZIT-UHFFFAOYSA-N LSM-1988 Chemical compound C1=CC(CN(C)C)=CC=C1C1=NC2=CC=CC3=C2N1CCNC3=O SEKJSSBJKFLZIT-UHFFFAOYSA-N 0.000 claims description 21
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 21
- 239000000375 suspending agent Substances 0.000 claims description 21
- KJQFBVYMGADDTQ-UHFFFAOYSA-N S-butyl-DL-homocysteine (S,R)-sulfoximine Chemical compound CCCCS(=N)(=O)CCC(N)C(O)=O KJQFBVYMGADDTQ-UHFFFAOYSA-N 0.000 claims description 20
- XIZCDQOKKYYCRH-UHFFFAOYSA-N 1h-benzimidazole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N)=NC2=C1 XIZCDQOKKYYCRH-UHFFFAOYSA-N 0.000 claims description 19
- ZKAMEFMDQNTDFK-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyrazine Chemical compound C1=CN=C2NC=NC2=N1 ZKAMEFMDQNTDFK-UHFFFAOYSA-N 0.000 claims description 19
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 19
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 19
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 19
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 claims description 19
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 claims description 19
- 229960001237 podophyllotoxin Drugs 0.000 claims description 19
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 claims description 19
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 claims description 19
- 108010092160 Dactinomycin Proteins 0.000 claims description 18
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 18
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 18
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 18
- 229960000640 dactinomycin Drugs 0.000 claims description 18
- 229950004354 phosphorylcholine Drugs 0.000 claims description 18
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 claims description 18
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 claims description 17
- OVBPIULPVIDEAO-LBPRGKRZSA-N Folic acid Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 17
- WJAJPNHVVFWKKL-UHFFFAOYSA-N Methoxamine Chemical compound COC1=CC=C(OC)C(C(O)C(C)N)=C1 WJAJPNHVVFWKKL-UHFFFAOYSA-N 0.000 claims description 17
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 17
- 229920000305 Nylon 6,10 Polymers 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 229960001231 choline Drugs 0.000 claims description 17
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 17
- 229960002626 clarithromycin Drugs 0.000 claims description 17
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 17
- 229960000304 folic acid Drugs 0.000 claims description 17
- 235000019152 folic acid Nutrition 0.000 claims description 17
- 239000011724 folic acid Substances 0.000 claims description 17
- 229960005192 methoxamine Drugs 0.000 claims description 17
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 claims description 17
- 229960004023 minocycline Drugs 0.000 claims description 17
- QRPFYXCKZRCRTD-UHFFFAOYSA-N 4-methyl-5-nitro-6-phenylmethoxypyrimidin-2-amine Chemical compound CC1=NC(N)=NC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O QRPFYXCKZRCRTD-UHFFFAOYSA-N 0.000 claims description 16
- DSIVLMKQNTVXOD-UHFFFAOYSA-N 5-nitro-4-phenylmethoxypyrimidin-2-amine Chemical compound NC1=NC=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=N1 DSIVLMKQNTVXOD-UHFFFAOYSA-N 0.000 claims description 16
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 16
- 239000002689 soil Substances 0.000 claims description 16
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims description 16
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims description 16
- HBJOXQRURQPDEX-MHXMMLMNSA-N (2s,4r)-n-[(1s,2s)-2-chloro-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-4-ethylpiperidine-2-carboxamide Chemical compound C1[C@H](CC)CCN[C@@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 HBJOXQRURQPDEX-MHXMMLMNSA-N 0.000 claims description 15
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims description 15
- GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 claims description 15
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 15
- KGTDRFCXGRULNK-UHFFFAOYSA-N Nogalamycin Natural products COC1C(OC)(C)C(OC)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=C4C5(C)OC(C(C(C5O)N(C)C)O)OC4=C3C3=O)=C3C=C2C(C(=O)OC)C(C)(O)C1 KGTDRFCXGRULNK-UHFFFAOYSA-N 0.000 claims description 15
- 108010057150 Peplomycin Proteins 0.000 claims description 15
- HXJDWCWJDCOHDG-RYUDHWBXSA-N S-hexylglutathione Chemical compound CCCCCCSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O HXJDWCWJDCOHDG-RYUDHWBXSA-N 0.000 claims description 15
- 229930192341 TAN-1518 Natural products 0.000 claims description 15
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 claims description 15
- 239000003005 anticarcinogenic agent Substances 0.000 claims description 15
- 229950006345 antramycin Drugs 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 15
- WLOHNSSYAXHWNR-NXPDYKKBSA-N dirithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H]2O[C@H](COCCOC)N[C@H]([C@@H]2C)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 WLOHNSSYAXHWNR-NXPDYKKBSA-N 0.000 claims description 15
- 229960004100 dirithromycin Drugs 0.000 claims description 15
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 claims description 15
- 229950009429 exatecan Drugs 0.000 claims description 15
- KGTDRFCXGRULNK-JYOBTZKQSA-N nogalamycin Chemical compound CO[C@@H]1[C@@](OC)(C)[C@@H](OC)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=C4[C@@]5(C)O[C@H]([C@H]([C@@H]([C@H]5O)N(C)C)O)OC4=C3C3=O)=C3C=C2[C@@H](C(=O)OC)[C@@](C)(O)C1 KGTDRFCXGRULNK-JYOBTZKQSA-N 0.000 claims description 15
- 229950009266 nogalamycin Drugs 0.000 claims description 15
- QIMGFXOHTOXMQP-GFAGFCTOSA-N peplomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCCN[C@@H](C)C=1C=CC=CC=1)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C QIMGFXOHTOXMQP-GFAGFCTOSA-N 0.000 claims description 15
- 229950003180 peplomycin Drugs 0.000 claims description 15
- 229960001635 pirlimycin Drugs 0.000 claims description 15
- XKLZIVIOZDNKEQ-CLQLPEFOSA-N sparsomycin Chemical compound CSC[S@](=O)C[C@H](CO)NC(=O)\C=C\C1=C(C)NC(=O)NC1=O XKLZIVIOZDNKEQ-CLQLPEFOSA-N 0.000 claims description 15
- 229950009641 sparsomycin Drugs 0.000 claims description 15
- XKLZIVIOZDNKEQ-UHFFFAOYSA-N sparsomycin Natural products CSCS(=O)CC(CO)NC(=O)C=CC1=C(C)NC(=O)NC1=O XKLZIVIOZDNKEQ-UHFFFAOYSA-N 0.000 claims description 15
- 235000012141 vanillin Nutrition 0.000 claims description 15
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 14
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 14
- VEKMHZIDYGAWJW-UHFFFAOYSA-N C(CCC)NO.[O] Chemical compound C(CCC)NO.[O] VEKMHZIDYGAWJW-UHFFFAOYSA-N 0.000 claims description 14
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 14
- 229910021529 ammonia Inorganic materials 0.000 claims description 14
- 102000001253 Protein Kinase Human genes 0.000 claims description 13
- 108060006633 protein kinase Proteins 0.000 claims description 13
- 229920000954 Polyglycolide Polymers 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 239000004633 polyglycolic acid Substances 0.000 claims description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 11
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 11
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 11
- JVYNJRBSXBYXQB-UHFFFAOYSA-N 4-[3-(4-carboxyphenoxy)propoxy]benzoic acid;decanedioic acid Chemical compound OC(=O)CCCCCCCCC(O)=O.C1=CC(C(=O)O)=CC=C1OCCCOC1=CC=C(C(O)=O)C=C1 JVYNJRBSXBYXQB-UHFFFAOYSA-N 0.000 claims description 10
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 10
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 10
- 229950004403 polifeprosan Drugs 0.000 claims description 10
- 239000000600 sorbitol Substances 0.000 claims description 10
- AOJJSUZBOXZQNB-UHFFFAOYSA-N 7-[(4-amino-5-hydroxy-6-methyl-2-oxanyl)oxy]-6,9,11-trihydroxy-9-(2-hydroxy-1-oxoethyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione Chemical compound C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(=O)CO)CC1OC1CC(N)C(O)C(C)O1 AOJJSUZBOXZQNB-UHFFFAOYSA-N 0.000 claims description 9
- 108010078777 Colistin Proteins 0.000 claims description 9
- 229930105110 Cyclosporin A Natural products 0.000 claims description 9
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 9
- 108010036949 Cyclosporine Proteins 0.000 claims description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 9
- 229960001265 ciclosporin Drugs 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000005038 ethylene vinyl acetate Substances 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims description 9
- YKQOSKADJPQZHB-YNWHQGOSSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1s)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O YKQOSKADJPQZHB-YNWHQGOSSA-N 0.000 claims description 9
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 9
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- ZBNJXSZNWZUYCI-UHFFFAOYSA-N octadecyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C ZBNJXSZNWZUYCI-UHFFFAOYSA-N 0.000 claims description 8
- 235000002949 phytic acid Nutrition 0.000 claims description 8
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 229960004275 glycolic acid Drugs 0.000 claims description 7
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N n-hexyl alcohol Natural products CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 7
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 7
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 claims description 6
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 229920002101 Chitin Polymers 0.000 claims description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 5
- 239000000194 fatty acid Substances 0.000 claims description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 5
- 229920001542 oligosaccharide Polymers 0.000 claims description 5
- 150000002482 oligosaccharides Chemical class 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 239000000811 xylitol Substances 0.000 claims description 5
- 235000010447 xylitol Nutrition 0.000 claims description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 5
- 229960002675 xylitol Drugs 0.000 claims description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- YADZBEISHVCBSJ-UHFFFAOYSA-N [I].OCC(O)CO Chemical compound [I].OCC(O)CO YADZBEISHVCBSJ-UHFFFAOYSA-N 0.000 claims description 4
- 210000004204 blood vessel Anatomy 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 229940083037 simethicone Drugs 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 210000001165 lymph node Anatomy 0.000 claims description 3
- 210000001685 thyroid gland Anatomy 0.000 claims description 3
- 201000000274 Carcinosarcoma Diseases 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000004696 endometrium Anatomy 0.000 claims description 2
- 210000003238 esophagus Anatomy 0.000 claims description 2
- 210000001508 eye Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 210000004907 gland Anatomy 0.000 claims description 2
- 238000002513 implantation Methods 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 210000005075 mammary gland Anatomy 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- 210000004877 mucosa Anatomy 0.000 claims description 2
- 210000001989 nasopharynx Anatomy 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 210000000664 rectum Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 210000004291 uterus Anatomy 0.000 claims description 2
- VUPBDWQPEOWRQP-RTUCOMKBSA-N [(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1S,2S)-3-[[(2R,3S)-5-[[(2S,3R)-1-[[2-[4-[4-[[4-amino-6-[3-(4-aminobutylamino)propylamino]-6-oxohexyl]carbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]-1-[(2S,3R,4R,5S,6S)-5-amino-3,4-dihydroxy-6-methyloxan-2-yl]oxy-2-hydroxyethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-5-oxopentan-2-yl]amino]-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate Chemical compound C[C@@H](O)[C@H](NC(=O)C[C@H](O)[C@@H](C)NC(=O)[C@@H](NC(=O)c1nc(nc(N)c1C)[C@H](CC(N)=O)NC[C@H](N)C(N)=O)[C@H](O[C@@H]1O[C@@H](CO)[C@@H](O)[C@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](OC(N)=O)[C@@H]1O)c1cnc[nH]1)C(=O)NC(O[C@@H]1O[C@@H](C)[C@@H](N)[C@@H](O)[C@H]1O)C(O)c1nc(cs1)-c1nc(cs1)C(=O)NCCCC(N)CC(=O)NCCCNCCCCN VUPBDWQPEOWRQP-RTUCOMKBSA-N 0.000 claims 3
- 108700003774 talisomycin Proteins 0.000 claims 3
- 229950002687 talisomycin Drugs 0.000 claims 3
- 241000196324 Embryophyta Species 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- ILFPCMXTASDZKM-YFKPBYRVSA-N (1s)-2-methylidene-3-oxocyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@H]1CCC(=O)C1=C ILFPCMXTASDZKM-YFKPBYRVSA-N 0.000 claims 1
- MNHVIVWFCMBFCV-AVGNSLFASA-N (2S)-2-[[(2S)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-6-diazo-5-oxohexanoyl]amino]-6-diazo-5-oxohexanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CCC(=O)C=[N+]=[N-])C(=O)N[C@@H](CCC(=O)C=[N+]=[N-])C(O)=O MNHVIVWFCMBFCV-AVGNSLFASA-N 0.000 claims 1
- LMGGOGHEVZMZCU-FGJMKEJPSA-N (2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-6,11-dioxo-3,4-dihydro-1h-tetracene-2-carboxylic acid Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(O)=O)C1 LMGGOGHEVZMZCU-FGJMKEJPSA-N 0.000 claims 1
- DLWOTOMWYCRPLK-UVTDQMKNSA-N (4z)-5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(4,5-dimethoxy-6-oxocyclohexa-2,4-dien-1-ylidene)-3-methyl-1h-pyridine-2-carboxylic acid Chemical compound C1=CC(OC)=C(OC)C(=O)\C1=C\1C(N)=C(C=2N=C3C(=O)C(N)=C(OC)C(=O)C3=CC=2)NC(C(O)=O)=C/1C DLWOTOMWYCRPLK-UVTDQMKNSA-N 0.000 claims 1
- FXMOIYLVKOALHC-MADCSZMMSA-N (6as,9s)-3,9-dihydroxy-2-methoxy-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound N1=C[C@@H]2CC[C@H](O)N2C(=O)C2=C1C=C(O)C(OC)=C2 FXMOIYLVKOALHC-MADCSZMMSA-N 0.000 claims 1
- OJRZEKJECRTBPJ-NGAMADIESA-N (z,5s)-5-acetamido-1-diazonio-6-hydroxy-6-oxohex-1-en-2-olate Chemical compound CC(=O)N[C@H](C(O)=O)CC\C([O-])=C\[N+]#N OJRZEKJECRTBPJ-NGAMADIESA-N 0.000 claims 1
- CKMBACZHCFMPLQ-DBRKOABJSA-N 2-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-selenazole-4-carboxamide Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 CKMBACZHCFMPLQ-DBRKOABJSA-N 0.000 claims 1
- QCXJFISCRQIYID-IAEPZHFASA-N 2-amino-1-n-[(3s,6s,7r,10s,16s)-3-[(2s)-butan-2-yl]-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-10-propan-2-yl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-9-n-[(3s,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propa Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N=C2C(C(=O)N[C@@H]3C(=O)N[C@H](C(N4CCC[C@H]4C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]3C)=O)[C@@H](C)CC)=C(N)C(=O)C(C)=C2O2)C2=C(C)C=C1 QCXJFISCRQIYID-IAEPZHFASA-N 0.000 claims 1
- AKSIYNOQZYMJED-UHFFFAOYSA-N 2-amino-4-(aminomethoxy)butanoic acid Chemical compound NCOCCC(N)C(O)=O AKSIYNOQZYMJED-UHFFFAOYSA-N 0.000 claims 1
- PWMYMKOUNYTVQN-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 PWMYMKOUNYTVQN-UHFFFAOYSA-N 0.000 claims 1
- GRLUHXSUZYFZCW-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine;dihydrochloride Chemical compound Cl.Cl.C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 GRLUHXSUZYFZCW-UHFFFAOYSA-N 0.000 claims 1
- ZGCSNRKSJLVANE-UHFFFAOYSA-N Aglycone-Rebeccamycin Natural products N1C2=C3NC4=C(Cl)C=CC=C4C3=C(C(=O)NC3=O)C3=C2C2=C1C(Cl)=CC=C2 ZGCSNRKSJLVANE-UHFFFAOYSA-N 0.000 claims 1
- 244000056139 Brassica cretica Species 0.000 claims 1
- 235000003351 Brassica cretica Nutrition 0.000 claims 1
- 235000003343 Brassica rupestris Nutrition 0.000 claims 1
- MKQWTWSXVILIKJ-LXGUWJNJSA-N Chlorozotocin Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NC(=O)N(N=O)CCCl MKQWTWSXVILIKJ-LXGUWJNJSA-N 0.000 claims 1
- RURLVUZRUFHCJO-UHFFFAOYSA-N Chromomycin A3 Natural products COC(C1Cc2cc3cc(OC4CC(OC(=O)C)C(OC5CC(O)C(OC)C(C)O5)C(C)O4)c(C)c(O)c3c(O)c2C(=O)C1OC6CC(OC7CC(C)(O)C(OC(=O)C)C(C)O7)C(O)C(C)O6)C(=O)C(O)C(C)O RURLVUZRUFHCJO-UHFFFAOYSA-N 0.000 claims 1
- SPKNARKFCOPTSY-UHFFFAOYSA-N D-asperlin Natural products CC1OC1C1C(OC(C)=O)C=CC(=O)O1 SPKNARKFCOPTSY-UHFFFAOYSA-N 0.000 claims 1
- 229930184584 Ditrisarubicin Natural products 0.000 claims 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- HQJNLDDXAFPBCM-UHFFFAOYSA-N Kidamycin Natural products CCC1OC(CC(NC)C1O)c2cc(C3CC(NC)C(O)C(CC)O3)c4C(=O)c5cc(CC)c6C(=O)C=C(Oc6c5C(=O)c4c2O)C(=CC)C HQJNLDDXAFPBCM-UHFFFAOYSA-N 0.000 claims 1
- 229930192392 Mitomycin Natural products 0.000 claims 1
- 229930187135 Olivomycin Natural products 0.000 claims 1
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- QEHOIJJIZXRMAN-UHFFFAOYSA-N Rebeccamycin Natural products OC1C(O)C(OC)C(CO)OC1N1C2=C3NC4=C(Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 QEHOIJJIZXRMAN-UHFFFAOYSA-N 0.000 claims 1
- OBZJZDHRXBKKTJ-UHFFFAOYSA-N Sangivamycin Natural products C12=NC=NC(N)=C2C(C(=O)N)=CN1C1OC(CO)C(O)C1O OBZJZDHRXBKKTJ-UHFFFAOYSA-N 0.000 claims 1
- GDVNLLJNADMLLR-BBRMVZONSA-N Spergualin Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)C[C@@H](O)CCCCN=C(N)N GDVNLLJNADMLLR-BBRMVZONSA-N 0.000 claims 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 claims 1
- SPKNARKFCOPTSY-XWPZMVOTSA-N [(2r,3s)-2-[(2s,3r)-3-methyloxiran-2-yl]-6-oxo-2,3-dihydropyran-3-yl] acetate Chemical compound C[C@H]1O[C@@H]1[C@H]1[C@@H](OC(C)=O)C=CC(=O)O1 SPKNARKFCOPTSY-XWPZMVOTSA-N 0.000 claims 1
- WYVYEIZFAUXWKW-SHUUXQFMSA-N [(2s,3s,4s,6r)-6-[[(1s,3s)-3-acetyl-3,5,10,12-tetrahydroxy-6,11-dioxo-2,4-dihydro-1h-tetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]azanium;chloride Chemical compound Cl.C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 WYVYEIZFAUXWKW-SHUUXQFMSA-N 0.000 claims 1
- RCQIFJCPIWRTAF-UHFFFAOYSA-N alazopeptin Chemical compound N#[N+]C=C([O-])CCC(C(=O)O)NC(=O)C(CCC([O-])=C[N+]#N)NCC=C RCQIFJCPIWRTAF-UHFFFAOYSA-N 0.000 claims 1
- 108010092626 allyl-(6-diazo-5-oxo)-norleucyl-(6-diazo-5-oxo)-norleucine Proteins 0.000 claims 1
- 108700016297 antibiotic 1588 Proteins 0.000 claims 1
- 229950004295 azotomycin Drugs 0.000 claims 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims 1
- 108010047824 bouvardin Proteins 0.000 claims 1
- TWOWSRSKGJSZHZ-VRHDFFKNSA-N bouvardin Chemical compound C1=CC(OC)=CC=C1C[C@H](N(C)C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N(C1=O)C)C2)C(=O)N[C@@H](C)C(=O)N(C)[C@H]1[C@@H](O)C(C=C1)=CC=C1OC1=CC2=CC=C1O TWOWSRSKGJSZHZ-VRHDFFKNSA-N 0.000 claims 1
- BNOCDYMCAVSRBT-UHFFFAOYSA-N bouvardin Natural products COc1ccc(CC2N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C3Cc4ccc(O)c(Oc5cccc(c5)C(O)C(N(C)C(=O)C(C)NC2=O)C(=O)N3C)c4)cc1 BNOCDYMCAVSRBT-UHFFFAOYSA-N 0.000 claims 1
- 108700002839 cactinomycin Proteins 0.000 claims 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 claims 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 claims 1
- 229960000975 daunorubicin Drugs 0.000 claims 1
- VGEBLZDDRJDVDP-AKAIEBDOSA-N demethylrifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C/C=C(C)/C(=O)NC2=C(O)C=3C(O)=C4C)C)OC)C4=C1C=3C(=O)\C2=C\NN1CCNCC1 VGEBLZDDRJDVDP-AKAIEBDOSA-N 0.000 claims 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 claims 1
- 229950005133 duazomycin Drugs 0.000 claims 1
- 229930192837 duazomycin Natural products 0.000 claims 1
- PLQKHNPZPRTISL-QSQNXQFYSA-N hitachimycin Chemical compound C1([C@H]2NC(=O)\C=C\C=C\C(\C)=C/[C@H]3C[C@@H](C(=C3C(=O)C[C@@H](O)CC/C=C/C2)O)OC)=CC=CC=C1 PLQKHNPZPRTISL-QSQNXQFYSA-N 0.000 claims 1
- MFTJRTUKCOVIMD-KUWIHEQQSA-N kidamycin Chemical compound OC1=C2C(=O)C3=C4OC(C(\C)=C/C)=CC(=O)C4=C(C)C=C3C(=O)C2=C([C@@H]2O[C@H](C)[C@@H](O)[C@H](C2)N(C)C)C=C1[C@H]1C[C@](C)(N(C)C)[C@H](O)[C@@H](C)O1 MFTJRTUKCOVIMD-KUWIHEQQSA-N 0.000 claims 1
- UFUYRGNJTFAODM-HQCAVAADSA-N macrocin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](O)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 UFUYRGNJTFAODM-HQCAVAADSA-N 0.000 claims 1
- HKZHTIOXLTVSKR-UHFFFAOYSA-N methyl 5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylate Chemical compound COC(=O)c1nc(c(N)c(c1C)-c1ccc(OC)c(OC)c1O)-c1ccc2C(=O)C(OC)=C(N)C(=O)c2n1 HKZHTIOXLTVSKR-UHFFFAOYSA-N 0.000 claims 1
- 229960004857 mitomycin Drugs 0.000 claims 1
- 235000010460 mustard Nutrition 0.000 claims 1
- FXMOIYLVKOALHC-UHFFFAOYSA-N neothramycin B Natural products N1=CC2CCC(O)N2C(=O)C2=C1C=C(O)C(OC)=C2 FXMOIYLVKOALHC-UHFFFAOYSA-N 0.000 claims 1
- CZDBNBLGZNWKMC-MWQNXGTOSA-N olivomycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1)O[C@H]1O[C@@H](C)[C@H](O)[C@@H](OC2O[C@@H](C)[C@H](O)[C@@H](O)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@H](O)[C@H](OC)[C@H](C)O1 CZDBNBLGZNWKMC-MWQNXGTOSA-N 0.000 claims 1
- 229950005848 olivomycin Drugs 0.000 claims 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims 1
- 229960002340 pentostatin Drugs 0.000 claims 1
- MYNIYCGOBKAQAO-UHFFFAOYSA-N piperazine;sulfuric acid Chemical compound OS(O)(=O)=O.C1CNCCN1 MYNIYCGOBKAQAO-UHFFFAOYSA-N 0.000 claims 1
- 229960004063 propylene glycol Drugs 0.000 claims 1
- MKSVFGKWZLUTTO-FZFAUISWSA-N puromycin dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO MKSVFGKWZLUTTO-FZFAUISWSA-N 0.000 claims 1
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 claims 1
- INSACQSBHKIWNS-QZQSLCQPSA-N rebeccamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](OC)[C@@H](CO)O[C@H]1N1C2=C3N=C4[C](Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 INSACQSBHKIWNS-QZQSLCQPSA-N 0.000 claims 1
- 229960005567 rebeccamycin Drugs 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 229950006216 rufocromomycin Drugs 0.000 claims 1
- OBZJZDHRXBKKTJ-JTFADIMSSA-N sangivamycin Chemical compound C12=NC=NC(N)=C2C(C(=O)N)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OBZJZDHRXBKKTJ-JTFADIMSSA-N 0.000 claims 1
- ILFPCMXTASDZKM-UHFFFAOYSA-N sarkomycin Natural products OC(=O)C1CCC(=O)C1=C ILFPCMXTASDZKM-UHFFFAOYSA-N 0.000 claims 1
- RAGFPHFDFVNLCG-INYQBOQCSA-N sibiromycin Chemical compound O[C@@H]1[C@@](O)(C)[C@@H](NC)[C@H](C)O[C@H]1OC(C(=C1O)C)=CC(C2=O)=C1N[C@H](O)[C@H]1N2C=C(\C=C\C)C1 RAGFPHFDFVNLCG-INYQBOQCSA-N 0.000 claims 1
- RAGFPHFDFVNLCG-UHFFFAOYSA-N sibiromycin Natural products OC1C(O)(C)C(NC)C(C)OC1OC(C(=C1O)C)=CC(C2=O)=C1NC(O)C1N2C=C(C=CC)C1 RAGFPHFDFVNLCG-UHFFFAOYSA-N 0.000 claims 1
- 229950006315 spirogermanium Drugs 0.000 claims 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims 1
- 229960001052 streptozocin Drugs 0.000 claims 1
- UJKRUPHWCPAJIL-CPLCKGKLSA-N zorbamycin Chemical compound N([C@H](C(=O)N[C@H](CCO)[C@@H](O)[C@H](C)C(=O)N[C@H](C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCC(N)=N)C(C)(C)O)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](C)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C UJKRUPHWCPAJIL-CPLCKGKLSA-N 0.000 claims 1
- 108010059327 zorbamycin Proteins 0.000 claims 1
- UJKRUPHWCPAJIL-UHFFFAOYSA-N zorbamycin Natural products N=1C(C=2SC=C(N=2)C(=O)NCCC(N)=N)CSC=1CCNC(=O)C(C(C)(C)O)NC(=O)C(C)C(O)C(CCO)NC(=O)C(C(OC1C(C(O)C(O)C(C)O1)OC1C(C(OC(N)=O)C(O)C(CO)O1)O)C=1NC=NC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C UJKRUPHWCPAJIL-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 65
- 239000000725 suspension Substances 0.000 abstract description 12
- 239000004615 ingredient Substances 0.000 abstract description 6
- 239000002671 adjuvant Substances 0.000 abstract description 5
- 230000001988 toxicity Effects 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 abstract 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 abstract 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 abstract 1
- 239000000470 constituent Substances 0.000 abstract 1
- 239000002532 enzyme inhibitor Substances 0.000 abstract 1
- 229940125532 enzyme inhibitor Drugs 0.000 abstract 1
- 229960000908 idarubicin Drugs 0.000 abstract 1
- 239000012747 synergistic agent Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 42
- 229940079593 drug Drugs 0.000 description 34
- 238000012360 testing method Methods 0.000 description 29
- 210000004881 tumor cell Anatomy 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- 230000002401 inhibitory effect Effects 0.000 description 16
- 230000004614 tumor growth Effects 0.000 description 15
- 230000012010 growth Effects 0.000 description 14
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 230000001629 suppression Effects 0.000 description 11
- 238000002156 mixing Methods 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 238000001694 spray drying Methods 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000011859 microparticle Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 238000010254 subcutaneous injection Methods 0.000 description 7
- 239000007929 subcutaneous injection Substances 0.000 description 7
- MHFRGQHAERHWKZ-HHHXNRCGSA-N (R)-edelfosine Chemical compound CCCCCCCCCCCCCCCCCCOC[C@@H](OC)COP([O-])(=O)OCC[N+](C)(C)C MHFRGQHAERHWKZ-HHHXNRCGSA-N 0.000 description 6
- PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 6
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 6
- CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 6
- 102000038030 PI3Ks Human genes 0.000 description 6
- 108091007960 PI3Ks Proteins 0.000 description 6
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 239000000693 micelle Substances 0.000 description 6
- 238000011275 oncology therapy Methods 0.000 description 6
- SZFPYBIJACMNJV-UHFFFAOYSA-N perifosine Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1 SZFPYBIJACMNJV-UHFFFAOYSA-N 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- GVPFIIZZKIULDY-GEMLJDPKSA-N (2s)-2-amino-5-[[(2r)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid;sulfane Chemical compound S.OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O GVPFIIZZKIULDY-GEMLJDPKSA-N 0.000 description 4
- 229920002732 Polyanhydride Polymers 0.000 description 4
- ODEDPKNSRBCSDO-UHFFFAOYSA-N [2-(hexadecylsulfanylmethyl)-3-methoxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCSCC(COC)COP([O-])(=O)OCC[N+](C)(C)C ODEDPKNSRBCSDO-UHFFFAOYSA-N 0.000 description 4
- 229920001400 block copolymer Polymers 0.000 description 4
- 238000007334 copolymerization reaction Methods 0.000 description 4
- 238000011978 dissolution method Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229950011461 edelfosine Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 229950006905 ilmofosine Drugs 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- KUAZQDVKQLNFPE-UHFFFAOYSA-N thiram Chemical compound CN(C)C(=S)SSC(=S)N(C)C KUAZQDVKQLNFPE-UHFFFAOYSA-N 0.000 description 4
- 229960002447 thiram Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 108091026813 Poly(ADPribose) Proteins 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 210000003716 mesoderm Anatomy 0.000 description 3
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 3
- 229960003775 miltefosine Drugs 0.000 description 3
- XBGNERSKEKDZDS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCN(C)C)=CC=CC3=CC2=C1 XBGNERSKEKDZDS-UHFFFAOYSA-N 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 208000023958 prostate neoplasm Diseases 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 238000011125 single therapy Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- CUQJLYFFQBHUGW-UHFFFAOYSA-N 2-(1-methylpiperidin-1-ium-1-yl)ethyl octadecyl phosphate Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+]1(C)CCCCC1 CUQJLYFFQBHUGW-UHFFFAOYSA-N 0.000 description 2
- NVVWVYYHTKCIAE-UHFFFAOYSA-N 2-(3'-methoxyphenyl) benzimidazole-4-carboxamide Chemical compound COC1=CC=CC(C=2NC3=CC=CC(=C3N=2)C(N)=O)=C1 NVVWVYYHTKCIAE-UHFFFAOYSA-N 0.000 description 2
- ZATXFBUSDJEEOC-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenyl]-1h-benzimidazole-4-carboxamide Chemical class N=1C=2C(C(=O)N)=CC=CC=2NC=1C1=CC=C(CO)C=C1 ZATXFBUSDJEEOC-UHFFFAOYSA-N 0.000 description 2
- OBBJGEVEIULNEO-UHFFFAOYSA-N 2-phenyl-1h-benzimidazole-4-carboxamide Chemical class N=1C=2C(C(=O)N)=CC=CC=2NC=1C1=CC=CC=C1 OBBJGEVEIULNEO-UHFFFAOYSA-N 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229920005576 aliphatic polyanhydride Polymers 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 238000007500 overflow downdraw method Methods 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 235000010603 pastilles Nutrition 0.000 description 2
- 229950010632 perifosine Drugs 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- XKZXGTOMPVMYOS-UHFFFAOYSA-N piperazine;propane Chemical compound CCC.C1CNCCN1 XKZXGTOMPVMYOS-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- RZNRKXGAJMGLIM-UHFFFAOYSA-N (3-hexadecoxy-2-methoxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCOCC(OC)COP([O-])(=O)OCC[N+](C)(C)C RZNRKXGAJMGLIM-UHFFFAOYSA-N 0.000 description 1
- YHKSBKQXCWHTQL-UHFFFAOYSA-N 1-[2-hydroxy-4-(4-morpholinyl)phenyl]ethanone Chemical compound C1=C(O)C(C(=O)C)=CC=C1N1CCOCC1 YHKSBKQXCWHTQL-UHFFFAOYSA-N 0.000 description 1
- UUIVKBHZENILKB-UHFFFAOYSA-N 2,2-dibromo-2-cyanoacetamide Chemical compound NC(=O)C(Br)(Br)C#N UUIVKBHZENILKB-UHFFFAOYSA-N 0.000 description 1
- ZCIUAKDSNQXBGM-UHFFFAOYSA-N 4-chloro-5-nitropyrimidin-2-amine Chemical compound NC1=NC=C([N+]([O-])=O)C(Cl)=N1 ZCIUAKDSNQXBGM-UHFFFAOYSA-N 0.000 description 1
- WJXQFVMTIGJBFX-UHFFFAOYSA-N 4-methoxytyramine Chemical compound COC1=CC=C(CCN)C=C1O WJXQFVMTIGJBFX-UHFFFAOYSA-N 0.000 description 1
- KDTRYSQLKJHLTJ-JKGXRCIZSA-N 5-bromo-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-iminopurin-6-one Chemical compound C12=NC(N)=NC(=O)C2(Br)N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 KDTRYSQLKJHLTJ-JKGXRCIZSA-N 0.000 description 1
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- OESOLVOZJGIVMY-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=C1C=CC=C2OC OESOLVOZJGIVMY-UHFFFAOYSA-N 0.000 description 1
- VLVHHGNPHBVEIG-UHFFFAOYSA-N 5-nitro-6-phenylmethoxypyrimidine-2,4-diamine Chemical compound NC1=NC(N)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=N1 VLVHHGNPHBVEIG-UHFFFAOYSA-N 0.000 description 1
- PBSHEZNAYNAEPU-UHFFFAOYSA-N 5-nitroso-6-phenylmethoxypyrimidine-2,4-diamine pyrimidine Chemical compound NC1=NC(=C(C(=N1)N)N=O)OCC1=CC=CC=C1.N1=CN=CC=C1 PBSHEZNAYNAEPU-UHFFFAOYSA-N 0.000 description 1
- HAYAYGFVSIWSGQ-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-3-hydroxyindeno[2,1-c]quinolin-7-one dihydrochloride Chemical compound Cl.Cl.C12=CC=CC=C2C(=O)C2=C1C1=CC=C(O)C=C1N=C2NCCN(C)C HAYAYGFVSIWSGQ-UHFFFAOYSA-N 0.000 description 1
- FXXUYUZEWHFQJZ-UHFFFAOYSA-N 6-phenylmethoxy-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(OCC=2C=CC=CC=2)=N1 FXXUYUZEWHFQJZ-UHFFFAOYSA-N 0.000 description 1
- USGXQONHRZESNF-JKGXRCIZSA-N 9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-imino-5-iodopurin-6-one Chemical compound IC12N=CN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC(=NC1=O)N USGXQONHRZESNF-JKGXRCIZSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- FTDYFMSUOXZKKR-UHFFFAOYSA-N C(C1=CC(=CC=C1)OC)C1=NC2=C(N1)C=CC=C2C(=O)N Chemical class C(C1=CC(=CC=C1)OC)C1=NC2=C(N1)C=CC=C2C(=O)N FTDYFMSUOXZKKR-UHFFFAOYSA-N 0.000 description 1
- SWGIHYLVNXNQSK-UHFFFAOYSA-N CCC.O=C1C(NCCN1)=O.O=C1C(NCCN1)=O Chemical compound CCC.O=C1C(NCCN1)=O.O=C1C(NCCN1)=O SWGIHYLVNXNQSK-UHFFFAOYSA-N 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 1
- 108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101001113483 Homo sapiens Poly [ADP-ribose] polymerase 1 Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 229920001273 Polyhydroxy acid Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- KCBDLLNCTLQLPL-UHFFFAOYSA-N acridine-4-carboxamide Chemical class C1=CC=C2N=C3C(C(=O)N)=CC=CC3=CC2=C1 KCBDLLNCTLQLPL-UHFFFAOYSA-N 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- SHDCBZUQYOSCFY-UHFFFAOYSA-N benzo[h]chromen-2-one Chemical compound C1=CC=CC2=C(OC(=O)C=C3)C3=CC=C21 SHDCBZUQYOSCFY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- ROWSTIYZUWEOMM-UHFFFAOYSA-N chembl488755 Chemical compound C12=CC=CC=C2C(=O)C2=C1C1=CC=C(O)C=C1N=C2NCCN(C)C ROWSTIYZUWEOMM-UHFFFAOYSA-N 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- LPRCVLBATUMNBP-UHFFFAOYSA-N decanedioic acid;propane Chemical compound CCC.OC(=O)CCCCCCCCC(O)=O LPRCVLBATUMNBP-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960004956 glycerylphosphorylcholine Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000012155 injection solvent Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000011806 microball Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- UVTPMAJGFRLLKF-UHFFFAOYSA-N o-(4-aminooxybutyl)hydroxylamine Chemical compound NOCCCCON UVTPMAJGFRLLKF-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000003361 porogen Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical compound CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- BETUMLXGYDBOLV-UHFFFAOYSA-N tetradecyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C BETUMLXGYDBOLV-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229920000785 ultra high molecular weight polyethylene Polymers 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
试验组(n) | 所受治疗 | 肿瘤体积(cm3) | P值 |
1(6) | 对照 | 68±10 | |
2(6) | 抗癌抗生素 | 52±5.0 | <0.05 |
3(6) | UCN-01 | 52±2.0 | <0.01 |
4(6) | UCN-02 | 48±2.2 | <0.01 |
5(6) | MIL | 58±5.2 | <0.01 |
6(6) | D-21266 | 40±3.0 | <0.01 |
7(6) | 抗癌抗生素+UCN-01 | 22±2.2 | <0.001 |
8(6) | 抗癌抗生素+UCN-02 | 30±3.8 | <0.001 |
9(6) | 抗癌抗生素+MIL | 32±3.6 | <0.001 |
10(6) | 抗癌抗生素+D-21266 | 18±2.0 | <0.001 |
瘤细胞 | 抗癌抗生素 | O4-BA | UCN-01 | UCN-02 | 抗癌抗生素+O4-BA | 抗癌抗生素+UCN-1 | 抗癌抗生素+UCN-2 |
CNS | 60% | 58% | 64% | 68% | 90% | 82% | 84% |
C6 | 64% | 64% | 60% | 64% | 94% | 80% | 94% |
SA | 54% | 62% | 56% | 62% | 86% | 92% | 92% |
BC | 54% | 64% | 54% | 64% | 94% | 82% | 82% |
BA | 58% | 60% | 62% | 60% | 92% | 92% | 92% |
LH | 62% | 58% | 62% | 58% | 90% | 86% | 84% |
PAT | 64% | 54% | 62% | 58% | 94% | 84% | 82% |
试验组(n) | 所受治疗 | 肿瘤体积(cm3) | P值 |
1(6) | 对照 | 80±10 | |
2(6) | ilmofosine | 48±5.3 | <0.05 |
3(6) | 抗癌抗生素 | 52±2.3 | <0.01 |
4(6) | ilmofosine+抗癌抗生素 | 30±2.6 | <0.001 |
5(6) | AMG-PC | 48±3.0 | <0.01 |
6(6) | AMG-PC+抗癌抗生素 | 26±3.0 | <0.001 |
7(6) | edelfosine | 30±2.8 | <0.01 |
8(6) | Edelfosine+抗癌抗生素 | 20±2.6 | <0.001 |
9(6) | IDOU | 30±3.2 | <0.01 |
10(6) | IDOU+抗癌抗生素 | 18±2.0 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 62 | <0.05 |
3(6) | 咪唑并哌嗪 | 26 | <0.01 |
4(6) | 咪唑并吡啶 | 28 | <0.01 |
5(6) | 渥曼青霉素 | 24 | <0.01 |
6(6) | 苯并吡喃 | 32 | <0.01 |
7(6) | 抗癌抗生素+咪唑并哌嗪 | 84 | <0.001 |
8(6) | 抗癌抗生素+咪唑并吡啶 | 88 | <0.001 |
9(6) | 抗癌抗生素+渥曼青霉素 | 88 | <0.001 |
10(6) | 抗癌抗生素+苯并吡喃 | 90 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 26 | <0.05 |
3(6) | LY294002 | 70 | <0.01 |
4(6) | SU11752 | 66 | <0.01 |
5(6) | SN-38 | 74 | <0.01 |
6(6) | OK-1035 | 66 | <0.01 |
7(6) | 抗癌抗生素+LY294002 | 90 | <0.001 |
8(6) | 抗癌抗生素+SU11752 | 86 | <0.001 |
9(6) | 抗癌抗生素+SN-38 | 88 | <0.001 |
10(6) | 抗癌抗生素+OK-1035 | 82 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 58 | <0.05 |
3(6) | 甲氧胺 | 50 | <0.05 |
4(6) | 二甲胺四环素 | 48 | <0.05 |
5(6) | 羟基胺 | 38 | <0.05 |
6(6) | O-甲基羟基胺 | 32 | <0.01 |
7(6) | 抗癌抗生素+甲氧胺 | 80 | <0.01 |
8(6) | 抗癌抗生素+二甲胺四环素 | 76 | <0.01 |
9(6) | 抗癌抗生素+羟基胺 | 88 | <0.01 |
10(6) | 抗癌抗生素+O-甲基羟基胺 | 86 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 52 | <0.05 |
3(6) | 3-AB | 46 | <0.01 |
4(6) | 苯甲酰胺 | 46 | <0.01 |
5(6) | PD128763 | 42 | <0.01 |
6(6) | AG14361 | 38 | <0.01 |
7(6) | 抗癌抗生素+3-AB | 88 | <0.001 |
8(6) | 抗癌抗生素+苯甲酰胺 | 78 | <0.001 |
9(6) | 抗癌抗生素+PD128763 | 94 | <0.001 |
10(6) | 抗癌抗生素+AG14361 | 86 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 50 | <0.05 |
3(6) | BZ1-6 | 50 | <0.01 |
4(6) | TI1-5 | 36 | <0.01 |
5(6) | TBC | 42 | <0.01 |
6(6) | 苯并咪唑 | 46 | <0.01 |
7(6) | 抗癌抗生素+BZ1-6 | 78 | <0.001 |
8(6) | 抗癌抗生素+TI1-5 | 88 | <0.001 |
9(6) | 抗癌抗生素+TBC | 78 | <0.001 |
10(6) | 抗癌抗生素+苯并咪唑 | 88 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 50 | <0.05 |
3(6) | NU1025 | 46 | <0.01 |
4(6) | PBC | 32 | <0.01 |
5(6) | MPBC | 46 | <0.01 |
6(6) | NU1085 | 42 | <0.01 |
7(6) | 抗癌抗生素+NU1025 | 78 | <0.001 |
8(6) | 抗癌抗生素+PBC | 86 | <0.001 |
9(6) | 抗癌抗生素+MPBC | 80 | <0.001 |
10(6) | 抗癌抗生素+NU1085 | 94 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 抗癌抗生素 | 60 | <0.05 |
3(6) | BSO | 46 | <0.01 |
4(6) | 氨基*** | 24 | <0.01 |
5(6) | 马勃菌酸 | 40 | <0.01 |
6(6) | 新鬼臼霉素 | 44 | <0.01 |
7(6) | 抗癌抗生素+BSO | 82 | <0.001 |
8(6) | 抗癌抗生素+氨基*** | 88 | <0.001 |
9(6) | 抗癌抗生素+马勃菌酸 | 76 | <0.001 |
10(6) | 抗癌抗生素+新鬼臼霉素 | 82 | <0.001 |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200610200171A CN1923171B (zh) | 2006-02-24 | 2006-02-24 | 同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200610200171A CN1923171B (zh) | 2006-02-24 | 2006-02-24 | 同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1923171A true CN1923171A (zh) | 2007-03-07 |
CN1923171B CN1923171B (zh) | 2010-05-19 |
Family
ID=37816115
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200610200171A Expired - Fee Related CN1923171B (zh) | 2006-02-24 | 2006-02-24 | 同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1923171B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104109247A (zh) * | 2013-01-15 | 2014-10-22 | 张雅珍 | 一种含有多柔比星结构的聚合物的制备和用途 |
US9701706B2 (en) | 2015-08-06 | 2017-07-11 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US11111264B2 (en) | 2017-09-21 | 2021-09-07 | Chimerix, Inc. | Morphic forms of 4-amino-7-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide and uses thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1079385A (zh) * | 1992-06-01 | 1993-12-15 | 丛繁滋 | 抗癌药物脂质体的制备方法 |
CN1561988A (zh) * | 2004-03-18 | 2005-01-12 | 山东居仁生物医药技术研究所 | 一种紫杉醇微球抗癌药物的制备方法 |
-
2006
- 2006-02-24 CN CN200610200171A patent/CN1923171B/zh not_active Expired - Fee Related
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104109247A (zh) * | 2013-01-15 | 2014-10-22 | 张雅珍 | 一种含有多柔比星结构的聚合物的制备和用途 |
CN104109247B (zh) * | 2013-01-15 | 2018-03-02 | 张雅珍 | 一种含有多柔比星结构的聚合物的制备和用途 |
US9701706B2 (en) | 2015-08-06 | 2017-07-11 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US9708359B2 (en) | 2015-08-06 | 2017-07-18 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US10407457B2 (en) | 2015-08-06 | 2019-09-10 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US10941175B2 (en) | 2015-08-06 | 2021-03-09 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US11981700B2 (en) | 2015-08-06 | 2024-05-14 | Chimerix, Inc. | Pyrrolopyrimidine nucleosides and analogs thereof |
US11111264B2 (en) | 2017-09-21 | 2021-09-07 | Chimerix, Inc. | Morphic forms of 4-amino-7-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
CN1923171B (zh) | 2010-05-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1857208A (zh) | 同载抗代谢药物及其增效剂的抗癌缓释注射剂 | |
CN1861050A (zh) | 一种同载铂类化合物及其增效剂的抗癌药物缓释注射剂 | |
CN1857221A (zh) | 一种同载铂类化合物及其增效剂的抗癌缓释剂 | |
CN1923171A (zh) | 同载抗癌抗生素及其增效剂的复方抗癌药物缓释剂 | |
CN1857217A (zh) | 一种含***受体拮抗剂的抗癌缓释注射剂 | |
CN1861047A (zh) | 同载血管抑制剂及其增效剂的抗癌药物缓释注射剂 | |
CN1861049A (zh) | 一种含吉西他滨的抗癌药物缓释注射剂 | |
CN1923173A (zh) | 一种同载抗癌抗生素及其增效剂的抗癌药物缓释剂 | |
CN1846679A (zh) | 含氨甲喋呤及其增效剂的缓释注射剂 | |
CN1846678A (zh) | 一种抗癌缓释注射剂 | |
CN1846687A (zh) | 一种含紫杉烷及其增效剂的缓释剂 | |
CN1857723A (zh) | 一种同载氨柔比星及其增效剂的抗癌药物缓释剂 | |
CN1846676A (zh) | 含氟尿嘧啶增效剂的缓释注射剂及其制备方法 | |
CN1857210A (zh) | 一种同载抗代谢药物及其增效剂的抗癌缓释剂 | |
CN1973823A (zh) | 一种含增效剂的抗癌组合物 | |
CN1850039A (zh) | 复方铂类药物缓释剂 | |
CN1846677A (zh) | 一种含氟尿嘧啶增效剂的缓释注射剂 | |
CN1919172A (zh) | 同载尼莫司汀及其增效剂的抗癌缓释剂 | |
CN1846673A (zh) | 含嘧啶类似物的抗癌药物缓释剂 | |
CN1875934A (zh) | 一种同载克罗拉滨及其增效剂的抗癌药物缓释注射剂 | |
CN1927179A (zh) | 一种含四唑紫罗兰的复方抗癌缓释注射剂 | |
CN1846674A (zh) | 抗癌药物缓释注射剂 | |
CN1887262A (zh) | 同载苯达莫司汀及其增效剂的抗癌药物缓释注射剂 | |
CN1923174A (zh) | 一种含抗癌抗生素的抗癌缓释注射剂 | |
CN1923286A (zh) | 一种同载抗癌抗生素及其增效剂的抗癌缓释剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee | ||
CP02 | Change in the address of a patent holder |
Address after: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee after: Jinan Kangquan Medicine Sci. & Tech. Co., Ltd. Address before: 206, room 2, building 19, Pioneer Park, No. 250100 Huaneng Road, Shandong, Ji'nan Patentee before: Jinan Kangquan Medicine Sci. & Tech. Co., Ltd. |
|
ASS | Succession or assignment of patent right |
Owner name: SHANDONG LANJIN BIOENGINEERING CO., LTD. Free format text: FORMER OWNER: JINAN KANGQUAN MEDICINE SCI. + TECH. CO., LTD. Effective date: 20120807 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20120807 Address after: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee after: Shandong Lanjin Pharmaceuticals Co., Ltd. Address before: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee before: Jinan Kangquan Medicine Sci. & Tech. Co., Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100519 Termination date: 20160224 |
|
CF01 | Termination of patent right due to non-payment of annual fee |