CN109550051A - Histone demethylase KDM6A inhibitor is in the purposes for preparing obesity treatment drugs - Google Patents
Histone demethylase KDM6A inhibitor is in the purposes for preparing obesity treatment drugs Download PDFInfo
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Abstract
The present invention provides a kind of histone demethylase KDM6A inhibitor and is preparing the purposes in obesity treatment drugs.Histone demethylase KDM6A inhibitor provided by the invention is able to suppress histone demethylase KDM6A activity, and then inhibits er stress related gene expression, leptin resistance is reduced, so that obesity be made to obtain medical treatment.
Description
Technical field
The present invention relates to field of biotechnology, are making more particularly to a kind of histone demethylase KDM6A inhibitor
The purposes of standby obesity treatment drugs.
Background technique
Fat illness rate worldwide increases year by year, and the research report U.S. has had 1/3 people to be in obesity.It is fat
It is numerous chronic uninfections such as important risk factor of diabetes B, cardiovascular disease and certain tumours, seriously endangers
Human health.Recent FDA is intended to reduce Energy intaking by appetite-suppressing by two kinds of novel slimming medicines.On the other hand, increase
Add energy consumption to intervene the fat attention increasingly by clinician and basic research personnel, finds energy consumption correlation factor
Have become the new hot spot of fat intervention study at present.
Lysine demethylase 6 (lysine demethylase 6, KDM6) family of histone demethylase contains
There is JMJC structural domain, and by removing dimethyl from Histone 3 lysine residue 27 (histone 3lysine 27, H3K27)
It is modified with trimethyl, to fight the EZH2 enzymatic activity in PRC2 compound.KDM6 family include KDM6A (also referred to as UTX) and
KDM6B (also referred to as JMJD3), and have been demonstrated to play an important role during various kinds of cell, including differentiation, aging, body are thin
Born of the same parents and reproduction cell reprogramming, inflammatory reaction and tumour.KDM6A takes part in growth and development, and it is thin to be also considered as acute lymphoblastic
One especially important target spot of born of the same parents' leukaemia (ALL) progression of disease.
However, physiological action of the KDM6A in other mankind's pathological conditions such as obesity has not been reported.
Summary of the invention
In view of the foregoing deficiencies of prior art, the purpose of the present invention is to provide a kind of histone demethylases
KDM6A inhibitor is preparing the purposes in obesity treatment drugs.
In order to achieve the above objects and other related objects, first aspect present invention provides histone demethylase KDM6A
Inhibitor is preparing the purposes in obesity treatment drugs.
In one embodiment, the histone demethylase KDM6A inhibitor refers to histone demethylation
Enzyme KDM6A has the molecule of inhibitory effect.
In one embodiment, the histone demethylase KDM6A inhibitor inhibition of histone demethylase
KDM6A activity or inhibition of histone demethylase KDM6A genetic transcription or expression.
In one embodiment, the histone demethylase KDM6A inhibitor includes KDM6A small molecule compound
Inhibitor, anti-KDM6A antibody, anti-KDM6A antisense nucleic acid and siRNA, the miRNA or ribozyme special to KDM6A.
In one embodiment, the NCBI accession number of the histone demethylase KDM6A albumen are as follows: NP_
066963。
The NCBI accession number of the histone demethylase KDM6A gene are as follows: NM_021140.
The obesity treatment drugs necessarily include histone demethylase KDM6A inhibitor, and go first with histone
Effective component of the base enzyme KDM6A inhibitor as aforementioned function.
The form of the obesity treatment drugs can be solid, liquid, gel, semi-fluid, aerosol etc. without specifically limited
Various material forms.
The obesity treatment drugs object to be directed to is mammal, such as rodent, primate, the mankind
Deng.
Second aspect of the present invention provides a kind of therapeutic agent of obesity, including a effective amount of histone demethylase
KDM6A inhibitor.
In one embodiment, the histone demethylase KDM6A inhibitor refers to histone demethylation
Enzyme KDM6A has the molecule of inhibitory effect.
In one embodiment, the histone demethylase KDM6A inhibitor inhibition of histone demethylase
KDM6A activity or inhibition of histone demethylase KDM6A genetic transcription or expression.
In one embodiment, the effective component of the therapeutic agent includes below one or more: small point of KDM6A
Sub- compound inhibitor, anti-KDM6A antibody, anti-KDM6A antisense nucleic acid and siRNA, the miRNA and ribozyme special to KDM6A.
In one embodiment, the drug further includes pharmaceutically acceptable carrier.
Third aspect present invention provides a kind of new application of histone demethylase KDM6A inhibitor, the histone
Demethylase KDM6A inhibitor inhibits promoter region H3K27Me3 expression, the inhibition endoplasm of er stress gene in preparation
The purposes of net stress level drug.
Fourth aspect present invention provides histone demethylase KDM6A as action target in screening bariatrician medicine
Purposes in object.
Fifth aspect present invention provides a kind of screening technique of obesity treatment drugs, comprising: whether verifies drug to be sieved
Histone demethylase KDM6A can be made to be suppressed, if so, it is determined as bariatrician drug candidate.
Further, which comprises
By drug effect to be sieved on the cell in vitro of expression histone demethylase KDM6A, determines and organize egg in cell
Whether white demethylase KDM6A is suppressed.
For example, screening mode can be with are as follows: carry out the training of the cell in vitro of expressing K DM6A under conditions of appropriate cell growth
It supports, two groups of comparative experimentss is set, and one group is added to drug to be sieved in the culture dish of the cell in vitro, another group of addition equivalent
Physiological saline, remaining condition is same, be incubated for, test cell in vitro KDM6A whether be suppressed.
The method that whether histone demethylase KDM6A has occurred vigor decline or expression decline in cell determined are as follows:
Real-time quantitative PCR and/or Western Blot detection or Mass Spectrometer Method.
Compared with prior art, the invention has the following beneficial effects:
Of the invention discloses the new application in obesity treatment drugs of histone demethylase KDM6A, this hair
The histone demethylase KDM6A inhibitor of bright offer is able to suppress histone demethylase KDM6A activity, and inhibition stress
The promoter region H3K27Me3 of gene is expressed, and is inhibited er stress horizontal, is reduced leptin resistance, obesity is made to obtain medical treatment.
Detailed description of the invention
Figure 1A: PCR analyzes and identifies Kdm6af/f, the genotype electrophoretogram of Cre/ERT2+ mouse.
Figure 1B: Kdm6a induction type knocks out conceptual scheme.
Fig. 1 C: verifying Kdm6a induction type is measured with PCR and knocks out result electrophoretogram.
Fig. 1 D: for detecting the glycaemic homeostasis in the obesity mice that high lipid food (high fat diet, HFD) is induced
OGTT measurement result figure.
Fig. 1 E: for checking DIO mouse to the ITT measurement result figure of the sensibility of insulin.
The glycaemic homeostasis result figure of Fig. 1 F:OGTT testing inspection standard diet mouse.
Fig. 1 G: the ITT test result figure for insulin sensitivity in check criteria diet mouse.
Fig. 2A: observation wild-type mice and Kdm6a induce weight and percent weight variation (figure in knockout type mouse 21 days
A is HFD mouse, carrier, n=10；GSK-J4, n=9).
Fig. 2 B: observation wild-type mice and Kdm6a induce weight and percent weight variation in knockout type mouse 21 days (general
Logical feed (normal diet, ND) mouse, carrier, n=10；GSK-J4, n=10)
Fig. 2 C: the representative figure of wild type and Kdm6a induction knockout type mouse is (left: wild type；Right Kdm6a induction knocks out
Type).
Fig. 2 D: changes of weight figure (p < 0.001 * * *；**p<0.005；*p<0.05.N.S. no significant difference is indicated).
Fig. 2 E: first week every intaking amount of solar eclipse thing (p < 0.001 * * * for the treatment of；**p<0.005；*p<0.05.N.S. indicate without
Significant difference).
Fig. 2 F: serum insulin concentration (p < 0.001 * * * of DIO mouse after treatment 3 weeks；**p<0.005；*p<0.05.
N.S. no significant difference is indicated).
Fig. 2 G: after treatment 3 weeks, Serum leptin levels (p < 0.001 * * * of DIO and ND mouse；**p<0.005；*p<
0.05.N.S. no significant difference is indicated).
Fig. 2 H: after treatment 3 weeks, total cholesterol density of serum (p < 0.001 * * * of DIO and ND mouse；**p<0.005；*p<
0.05.N.S. no significant difference is indicated).
Specific embodiment
Er stress and fat pathophysiological mechanism are closely related.The increase of endoplasmic reticulum is in leptin resistance in brain
Key effect is played in development, can induce obesity.As described above, the histone demethylase KDM6A that discloses of the invention exists
The new application in obesity treatment drugs is prepared, histone demethylase KDM6A inhibitor provided by the invention is able to suppress
Histone demethylase KDM6A activity, inhibits the promoter region H3K27Me3 of stress gene to express, inhibits er stress water
It is flat, leptin resistance is reduced, obesity is made to obtain medical treatment.
Histone demethylase KDM6A inhibitor
Refer to the molecule that there is inhibitory effect for histone demethylase KDM6A.For histone demethylase
KDM6A includes but is not limited to inhibitory effect: inhibition of histone demethylase KDM6A activity or inhibition of histone are gone
Methylase KDM6A genetic transcription or expression.The histone demethylase KDM6A inhibitor include but is not limited to siRNA,
ShRNA, antibody, small molecule compound.
Inhibition of histone demethylase KDM6A activity is that histone demethylase KDM6A vigor is instigated to decline.It is preferred that
Ground, before inhibiting, histone demethylase KDM6A vigor decline at least 10% preferably reduces at least 30%, then good
At least 50% is reduced, more preferably reduces at least 70%, optimal reduction at least 90%.
Inhibition of histone demethylase KDM6A genetic transcription or expression refer to: making histone demethylase KDM6A's
Gene is not transcribed, or reduces the transcriptional activity of the gene of histone demethylase KDM6A, or make histone demethylase
The gene of KDM6A is not expressed, or reduces the expression activity of the gene of histone demethylase KDM6A.
Genetic transcription or expression of the conventional method to histone demethylase KDM6A can be used in those skilled in the art
It is adjusted, such as gene knockout, homologous recombination, RNA interfering etc..
The inhibition of genetic transcription or the expression of histone demethylase KDM6A can pass through PCR and Western Blot
Detect expression quantity verifying.
Preferably, compared with wild type, histone demethylase KDM6A genetic transcription or expression reduce at least 10%,
At least 30%, then good reduction at least 50% are preferably reduced, at least 70%, and good reduction at least 90% are more preferably reduced,
Most preferably histone demethylase KDM6A gene is absolutely not expressed.
Micromolecular compound inhibitor
Middle finger of the present invention is made of several or tens atoms, and molecular mass is in 1000 compounds below.
Histone demethylase KDM6A inhibitor prepares drug
Medicine is prepared using histone demethylase KDM6A inhibitor as one of main active or main active
Object.In general, in drug other than effective component, according to the needs of different dosage forms, will also include one or more can pharmaceutically be connect
The carrier or auxiliary material received.
" pharmaceutically acceptable " refers to that they will not be produced when biomolecule ontology and composition suitably give animal or people
Raw unfavorable, allergy or other adverse reactions.
" pharmaceutically acceptable carrier or auxiliary material " should be compatible with histone demethylase KDM6A inhibitor, can
The blended effect without pharmaceutical composition is greatly lowered in general.It can be used as pharmaceutically acceptable carrier
Or the specific example of some substances of auxiliary material is carbohydrate, such as lactose, dextrose and saccharose；Starch, as cornstarch and potato form sediment
Powder；Cellulose and its derivates, such as sodium carboxymethylcellulose pyce, ethyl cellulose and methylcellulose；Tragacanth powder；Malt；
Gelatin；Talcum；Solid lubricant, such as stearic acid and magnesium stearate；Calcium sulfate；Vegetable oil, as peanut oil, cottonseed oil, sesame oil,
Olive oil, corn oil and cupu oil；Polyalcohol, such as the third two liquor-saturated, glycerol, D-sorbite, mannitol and polyethylene glycol；Seaweed
Acid；Emulsifier, such as Tween；Wetting agent, such as NaLS；Colorant；Flavoring agent；Tablet agent, stabilizer；Antioxidant；
Preservative；Apirogen water；Isotonic salting liquid；With phosphate buffer etc..These substances are used to help the steady of formula as needed
It is qualitative or help to improve activity or it biological effectiveness or acceptable mouthfeel or smell are generated in the case where oral.
In the present invention, unless stated otherwise, pharmaceutical dosage form is not particularly limited, and can be made into injection, oral solution, piece
The dosage forms such as agent, capsule, dripping pill, spray can be prepared by conventional method.The selection of pharmaceutical dosage form should be with administration mode phase
Match.
Illustrate embodiments of the present invention below by way of specific specific example, those skilled in the art can be by this specification
Other advantages and efficacy of the present invention can be easily understood for disclosed content.The present invention can also pass through in addition different specific realities
The mode of applying is embodied or practiced, the various details in this specification can also based on different viewpoints and application, without departing from
Various modifications or alterations are carried out under spirit of the invention.
Before further describing the specific embodiments of the present invention, it should be appreciated that protection scope of the present invention is not limited to down
State specific specific embodiment；It is also understood that term used in the embodiment of the present invention is specific specific in order to describe
Embodiment, rather than limiting the scope of protection of the present invention；In description of the invention and claims, unless in text
In addition explicitly point out, singular "one", " one " and " this " include plural form.
When embodiment provides numberical range, it should be appreciated that except non-present invention is otherwise noted, two ends of each numberical range
Any one numerical value can be selected between point and two endpoints.Unless otherwise defined, the present invention used in all technologies and
Scientific term is identical as the normally understood meaning of those skilled in the art of the present technique.Except specific method, equipment used in embodiment,
Outside material, grasp and record of the invention according to those skilled in the art to the prior art can also be used and this
Any method, equipment and the material of the similar or equivalent prior art of method described in inventive embodiments, equipment, material come real
The existing present invention.
Unless otherwise stated, disclosed in this invention experimental method, detection method, preparation method be all made of this technology neck
Molecular biology, biochemistry, chromatin Structure and the analysis of domain routine, analytical chemistry, cell culture, recombinant DNA technology and
The routine techniques of related fields.
Embodiment 1KDM6A lacks the influence to Diet-Induced Obesity (DIO) mouse weight
Related with obesity in view of er stress, in order to study the potential physiological effect of KDM6A in vivo, we are established
Inducible genes knock-out mice, and the obese model for having selected high fat diet to induce, mouse histone demethylase Kdm6a's
NCBI accession number are as follows: NM_009483.
1.1 experimental animal
Kdm6af/f(1) (U.S. laboratory Jackson preservation number 024177) and UBC-Cre/ERT2 (2) (U.S.
007179) two mouse species have been reported that the preservation number of the laboratory Jackson before.Two Strains of Mouse are all small with C57 wild type
Mouse backcrossing 10 is more than generation.Kdm6aiKO/YMouse is bred by above two breeding line mating, reacts identification genotype using PCR,
The mouse can knock out to inductivity the Kdm6a gene in systemic body-wide after receiving tamoxifen injection.Mouse is raised 22
DEG C, in the no-special pathogen environment of 12 hours day-night cycles, free feeding and drinking-water.
1.2 grouping
Experimental animal is divided into four groups, and one group knocks out Kdm6a for inductioniKO/YMouse 10 (high fat diet), another group is
Wild type Kdm6aWT/YMouse 10 (high fat diet)；One group knocks out Kdm6a for inductioniKO/YMouse 10 (standard diet), separately
One group is wild type Kdm6aWT/YMouse 10 (standard diet).
1.3 experimental method
High lipid food nursing (60kcal% lipid is carried out since 6 week old；Research Diets formulas
D12492；Research Diets, Inc., New Brunswick, NJ) or fed standard chow (11kcal% lipid；
Research Diets formulas D12329；Research Diets, Inc.), continue 16 weeks.It weighs weekly, 16
After week in order to induce knock out Kdm6a, continuous 4 days using intraperitoneal injection tamoxifen (150 μ l, 10 μ g/ μ l of solution concentration, quite
In dosage be 75mg/kg) to activate Cre/ERT2 recombinase, to knock out KDM6A gene.3 weeks after tamoxifen injection, animal
Materials, collection blood and tissue after anesthesia is put to death.
1.3.1OGTT sugar tolerance is tested
Animal takes orally injectable dextrose monohydrate 1g/kg by after hungry 15 hours.Blood is detected by hand-held blood glucose meter after the blood of tail portion
Sugar, testing time point are respectively 15,30,60,90 and 120 minutes before and after taking orally injectable dextrose monohydrate.
1.3.2ITT sugar tolerance is tested
Animal by from early 8 up to afternoon 2 when it is 6 hours hungry after, insulin 1IU/kg is injected intraperitoneally.Tail portion takes after blood by hand
Formula blood glucose meter detection blood glucose is held, testing time point is respectively 15,30,45 and 60 minutes before and after injecting.
1.3.3 Serum Indexes detect
Using the leptin (R&D), insulin (Millipore), cholesterol in ELISA method detection serum
(Roche)and triglyceride(Roche)。
1.4 as the result is shown
Kdm6a is analyzed and identified by PCRf/f,Cre/ERT2+The genotype (Figure 1A) of mouse.With the small of verifying genotype
Mouse takes tamoxifen daily and is injected intraperitoneally 4 days, lead to the function activation of CRE/ERT2 to knock out Kdm6a gene (Figure 1B,
C).It is worth noting that, the induction knockout of KDM6A significantly reduces the weight (Fig. 2A) of DIO mouse.It is being administered after three weeks most
One day after, Kdm6aiKO/YLow nearly 30% (Fig. 2 B, C) of weight before the weight ratio treatment of mouse.Consistently therewith, KDM6A
Knockout significantly reduces kidney week and epididymal adipose compared with wild type high fat diet group (Fig. 2 D).We have also investigated
Influence of the KDM6A gene knockout to normal diet mouse weight.It is controlled by the tamoxifen with high fat diet group same dose
After treatment, normal diet Kdm6aiKO/YThe weight of mouse and the weight of wild-type mice are suitable.
The main reason for due to the decline of food intake dose being weight loss, the present invention measures drug treatment second week
Average food intake.Kdm6aiKO/YThe Kdm6a of the quantity of food ratio DIO mouse of mouse consumptionWT/YGroup much lower (Fig. 2 D).This
Inventing also found, Kdm6aiKO/YThe concentration of insulin and leptin ratio Kdm6a in mouseWT/YMouse (Fig. 2 E, F) is much lower.KDM6A
Knock out the metabolism state (Fig. 2 G) for being obviously improved DIO mouse.Although the food intake dose of normal diet mouse significantly reduces,
Tamoxifen knockout is given after Kdm6a 3 weeks, compared with wild type group, insulin, leptin or total cholesterol level be not significant
Variation.In OGTT analysis, the induction of KDM6A knocks out the glucose homeostasis (Fig. 1 D) for selectively enhancing obesity mice, without
It can influence modest mouse (Fig. 1 F).Either in the ITT analysis of obesity mice or modest mouse, Kdm6a is knocked out to insulin stimulating
No conspicuousness influences (Fig. 1 E, G).
In conclusion the ingesting of obesity-induced mice high in fat, weight can be substantially reduced by knocking out KDM6A, KDM6A is treatment
The drug target of obesity, KDM6A inhibitor can be used for treating obesity.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology all without departing from the spirit and scope of the present invention, carries out modifications and changes to above-described embodiment.Cause
This, institute is complete without departing from the spirit and technical ideas disclosed in the present invention by those of ordinary skill in the art such as
At all equivalent modifications or change, should be covered by the claims of the present invention.
Claims (10)
1. a kind of histone demethylase KDM6A inhibitor is preparing the purposes in obesity treatment drugs.
2. purposes as described in claim 1, which is characterized in that the histone demethylase KDM6A inhibitor refers to pair
Histone demethylase KDM6A has the molecule of inhibitory effect.
3. purposes as described in claim 1, which is characterized in that the histone demethylase KDM6A inhibitor inhibition group
Albumen demethylase KDM6A activity or inhibition of histone demethylase KDM6A genetic transcription or expression.
4. purposes as described in claim 1, which is characterized in that the histone demethylase KDM6A inhibitor includes
KDM6A micromolecular compound inhibitor, anti-KDM6A antibody, anti-KDM6A antisense nucleic acid and to KDM6A special siRNA,
MiRNA or ribozyme.
5. purposes as described in claim 1, which is characterized in that the NCBI accession number of the histone demethylase KDM6A
Are as follows: NP_066963.
6. a kind of therapeutic agent of obesity, including a effective amount of histone demethylase KDM6A inhibitor.
7. a kind of new application of histone demethylase KDM6A inhibitor, the histone demethylase KDM6A inhibitor
Inhibit the promoter region H3K27Me3 expression of er stress gene, the purposes of the inhibition horizontal drug of er stress in preparation.
8. purposes of the histone demethylase KDM6A as action target in screening obesity treatment drugs.
9. a kind of screening technique of obesity treatment drugs, comprising: verify whether drug to be sieved can make histone demethylase
KDM6A is suppressed, if so, it is determined as bariatrician drug candidate.
10. the screening technique of obesity treatment drugs as claimed in claim 9, which is characterized in that the described method includes: will be to
Drug effect is sieved on the cell in vitro of expression histone demethylase KDM6A, determines histone demethylase in cell
Whether KDM6A is suppressed.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113599522A (en) * | 2021-08-03 | 2021-11-05 | 武汉大学 | Application of KDM6 as target in preparation of medicine for improving differentiation efficiency of early neuroectoderm |
| CN114522233A (en) * | 2021-11-30 | 2022-05-24 | 首都医科大学附属北京口腔医院 | Polypeptide sequence of KDM6B and regulation and control application to mesenchymal stem cell function |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104174021A (en) * | 2013-05-22 | 2014-12-03 | 复旦大学附属华山医院 | Application of proteasome inhibitors in preparation of medicine for curing chronic lower-grade inflammation diseases |
| WO2017099829A1 (en) * | 2015-12-11 | 2017-06-15 | The General Hospital Corporation | Compositions and methods for treating drug-tolerant glioblastoma |
| CN106906217A (en) * | 2017-03-01 | 2017-06-30 | 中国人民解放军第二军医大学 | Suppress siRNA and its application of Kdm6a gene expressions |
| CN107096015A (en) * | 2017-03-01 | 2017-08-29 | 中国人民解放军第二军医大学 | The antivirus action of novel antiviral molecule Kdm6a a kind of and its application |
| CN108220422A (en) * | 2018-01-05 | 2018-06-29 | 武汉大学 | Application of the histone demethylase in screening treatment fatty liver and its relevant disease drug |
-
2019
- 2019-01-31 CN CN201910098757.1A patent/CN109550051B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104174021A (en) * | 2013-05-22 | 2014-12-03 | 复旦大学附属华山医院 | Application of proteasome inhibitors in preparation of medicine for curing chronic lower-grade inflammation diseases |
| WO2017099829A1 (en) * | 2015-12-11 | 2017-06-15 | The General Hospital Corporation | Compositions and methods for treating drug-tolerant glioblastoma |
| CN106906217A (en) * | 2017-03-01 | 2017-06-30 | 中国人民解放军第二军医大学 | Suppress siRNA and its application of Kdm6a gene expressions |
| CN107096015A (en) * | 2017-03-01 | 2017-08-29 | 中国人民解放军第二军医大学 | The antivirus action of novel antiviral molecule Kdm6a a kind of and its application |
| CN108220422A (en) * | 2018-01-05 | 2018-06-29 | 武汉大学 | Application of the histone demethylase in screening treatment fatty liver and its relevant disease drug |
Non-Patent Citations (2)
| Title |
|---|
| MIN GYU LEE ET AL: "Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination", 《SCIENCE》 * |
| XIA LI ET AL: "Demethylase Kdm6a epigenetically promotes IL-6 and IFN-b production in macrophages", 《JOURNAL OF AUTOIMMUNITY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113599522A (en) * | 2021-08-03 | 2021-11-05 | 武汉大学 | Application of KDM6 as target in preparation of medicine for improving differentiation efficiency of early neuroectoderm |
| CN113599522B (en) * | 2021-08-03 | 2022-09-20 | 深圳市北科生物科技有限公司 | Application of KDM6 as target in preparation of medicine for improving differentiation efficiency of early neuroectoderm |
| CN114522233A (en) * | 2021-11-30 | 2022-05-24 | 首都医科大学附属北京口腔医院 | Polypeptide sequence of KDM6B and regulation and control application to mesenchymal stem cell function |
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