CN117695395A - Application of H3K36ac inhibitor in preparation of medicine for treating obesity - Google Patents
Application of H3K36ac inhibitor in preparation of medicine for treating obesity Download PDFInfo
- Publication number
- CN117695395A CN117695395A CN202410160071.1A CN202410160071A CN117695395A CN 117695395 A CN117695395 A CN 117695395A CN 202410160071 A CN202410160071 A CN 202410160071A CN 117695395 A CN117695395 A CN 117695395A
- Authority
- CN
- China
- Prior art keywords
- h3k36ac
- obesity
- acetylation
- inhibitor
- agents
- 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.)
- Pending
Links
- 208000008589 Obesity Diseases 0.000 title claims abstract description 50
- 235000020824 obesity Nutrition 0.000 title claims abstract description 50
- 239000003112 inhibitor Substances 0.000 title claims abstract description 19
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims description 4
- 230000021736 acetylation Effects 0.000 claims abstract description 38
- 238000006640 acetylation reaction Methods 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 11
- 210000000577 adipose tissue Anatomy 0.000 claims description 34
- 210000001789 adipocyte Anatomy 0.000 claims description 15
- 239000003147 molecular marker Substances 0.000 claims description 12
- 230000037396 body weight Effects 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- YYTHPXHGWSAKIZ-UHFFFAOYSA-N cyclopentylidene-[4-(4-chlorophenyl)thiazol-2-yl]hydrazone Chemical compound C1=CC(Cl)=CC=C1C1=CSC(NN=C2CCCC2)=N1 YYTHPXHGWSAKIZ-UHFFFAOYSA-N 0.000 claims description 6
- -1 glidants Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 238000009007 Diagnostic Kit Methods 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 239000002250 absorbent Substances 0.000 claims description 2
- 230000002745 absorbent Effects 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- 229930188620 butyrolactone Natural products 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 239000008394 flocculating agent Substances 0.000 claims description 2
- 239000004088 foaming agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims description 2
- 239000003906 humectant Substances 0.000 claims description 2
- 230000010354 integration Effects 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000003094 microcapsule Substances 0.000 claims description 2
- 239000004005 microsphere Substances 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 230000003204 osmotic effect Effects 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 239000004014 plasticizer Substances 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- 239000003380 propellant Substances 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000000375 suspending agent Substances 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- 239000002562 thickening agent Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 230000000181 anti-adherent effect Effects 0.000 claims 1
- 239000006184 cosolvent Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 108020004999 messenger RNA Proteins 0.000 abstract description 9
- 230000037356 lipid metabolism Effects 0.000 abstract description 8
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 230000006372 lipid accumulation Effects 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 5
- 230000005764 inhibitory process Effects 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 27
- 108010033040 Histones Proteins 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 14
- 230000006698 induction Effects 0.000 description 12
- 239000002609 medium Substances 0.000 description 10
- 238000010186 staining Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 238000013116 obese mouse model Methods 0.000 description 9
- 102000006947 Histones Human genes 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 102100033636 Histone H3.2 Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 235000009200 high fat diet Nutrition 0.000 description 7
- 101710195387 Histone H3.2 Proteins 0.000 description 6
- 101710195400 Histone H3.3 Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 208000016261 weight loss Diseases 0.000 description 6
- 108010033276 Peptide Fragments Proteins 0.000 description 5
- 102000007079 Peptide Fragments Human genes 0.000 description 5
- 235000021590 normal diet Nutrition 0.000 description 5
- 230000004481 post-translational protein modification Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 4
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 4
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 4
- 239000005642 Oleic acid Substances 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 238000011532 immunohistochemical staining Methods 0.000 description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 4
- 238000013227 male C57BL/6J mice Methods 0.000 description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 101001011741 Bos taurus Insulin Proteins 0.000 description 3
- 102100034535 Histone H3.1 Human genes 0.000 description 3
- 206010020880 Hypertrophy Diseases 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 230000004132 lipogenesis Effects 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 238000010839 reverse transcription Methods 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108010047956 Nucleosomes Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000030944 contact inhibition Effects 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 230000006195 histone acetylation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 210000001623 nucleosome Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 239000013585 weight reducing agent Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- YOQUZCNSUOJWQS-UHFFFAOYSA-N 3-chloro-4-methylaniline;hydron;chloride Chemical compound Cl.CC1=CC=C(N)C=C1Cl YOQUZCNSUOJWQS-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 244000050510 Cunninghamia lanceolata Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 102100039869 Histone H2B type F-S Human genes 0.000 description 1
- 101710195388 Histone H3.1 Proteins 0.000 description 1
- 229940122597 Histone acetyltransferase inhibitor Drugs 0.000 description 1
- 102000003893 Histone acetyltransferases Human genes 0.000 description 1
- 108090000246 Histone acetyltransferases Proteins 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 101100102907 Mus musculus Wdtc1 gene Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 208000001280 Prediabetic State Diseases 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009815 adipogenic differentiation Effects 0.000 description 1
- 230000002293 adipogenic effect Effects 0.000 description 1
- 210000000593 adipose tissue white Anatomy 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 238000010201 enrichment analysis Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000013427 histology analysis Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006759 inflammatory activation Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Abstract
The invention relates to an application of an H3K36ac inhibitor in preparing a medicament for treating obesity, and belongs to the technical field of biological medicines. The invention provides an application of an inhibitor for inhibiting H3K36ac acetylation in preparing a medicament for preventing and/or treating obesity and/or obesity-related diseases. The research shows that the inhibition of the acetylation level of H3K36ac has the effects of reducing lipid accumulation and up-regulating the level of lipid metabolism gene PPAR mRNA, so that the H3K36ac can be used as a new target for preventing and treating obesity, and the inhibitor for inhibiting the acetylation of H3K36ac has great application prospect in preparing medicines for preventing and/or treating obesity and/or obesity related diseases.
Description
Technical Field
The invention relates to an application of an H3K36ac inhibitor in preparing a medicament for treating obesity, and belongs to the technical field of biological medicines.
Background
Obesity is mainly characterized by excessive weight gain and lipid accumulation. Studies have reported that obesity has become an independent risk factor for a variety of metabolic and cardiovascular diseases (see, for example, the literature "Powell-Wiley, t.m., et al,Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association.circulation, 2021.143 (21): p.e 984-e1010, "and" blue, m.,Obesity: global epidemiology and pathogenesis.nat Rev Endocrinol, 2019.15 (5): p.288-298 "). Adipose tissue has important regulation and control effects on metabolic disorder, inflammatory activation and the like caused by obesity. In obesity, adipose tissue not only stores excessive lipids, but also has endocrine function, and the generated fat factors can mediate the occurrence of insulin resistance and other mechanisms, resulting in disorder of in vivo metabolism. Therefore, prevention and treatment of obesity are important for maintaining human health.
Currently, methods for preventing and treating obesity are limited. Clinical studies have found that enhanced lifestyle interventions are an effective treatment for controlling obesity and obesity-related disorders, which can significantly improve obesity. Lifestyle-enhancing interventions are mainly those involving limiting energy intake, increasing physical activity in two levels to achieve a 10% weight loss (see, for example, documents "bands, m.p., et al,Type 2 Diabetes Subgroups, Risk for Complications, and Differential Effects Due to an Intensive Lifestyle Intervention.diabetes Care, 2021.44 (5): p.1203-1210 and "beans, J.W., et al,Dietary weight loss- induced improvements in metabolic function are enhanced by exercise in people with obesity and prediabetes.nat Metab, 2023.5 (7): p.1221-1235 "). However, intensive lifestyle interventions require at least more than 1 year of intervention time, and long-term compliance is not good, and weight recovery after lifestyle intervention is common. At present, the national approval of auxiliary weight-loss drugs is still limited, and clinically used indexes require that the BMI of obese patients exceeds 30kg/m 2 . Thus, there is a great need to find more potential for obesityPreventive and therapeutic agents.
Disclosure of Invention
To solve the problems, the invention provides application of an inhibitor for inhibiting H3K36ac acetylation in preparing a medicament for preventing and/or treating obesity and/or obesity-related diseases.
Histones (histones) are basic proteins in eukaryotic and prokaryotic cells that together with DNA constitute the nucleosome structure. The N-terminal part of the histone protein does not participate in nucleosome assembly, but protrudes from the core structure, is more suitable for interaction with the adjacent environment, and is therefore susceptible to post-translational modification (PTM). Histone PTMs include methylation, acetylation, phosphorylation, ubiquitination, ADP ribosylation, and the like. Wherein, histone acetylation refers to a process of adding acetyl group to histone lysine residue under the action of acetyl transferase. In organisms, the two processes of acetylation and deacetylation are in dynamic balance, and transcriptional expression of genes is regulated together. Typically, histone acetylation activates gene expression, whereas deacetylation inhibits gene expression. The effects of acetylation occurring at different lysine sites of histones on gene expression function are different. H3K36ac refers to the acetylation modification at the position of lysine 36 of histone 3 (H3). The level of H3K36ac acetylation refers to the degree of acetylation modification of lysine 36 of histone 3. Typically, the level of acetylation of histones is co-regulated by histone acetylases and deacetylases.
In one embodiment of the invention, the H3K36ac comprises h3.1k36ac, h3.2k36ac, and/or h3.3k36ac. There are various variant forms of histone, among which there are 3 variants of H3, H3.1, H3.2 and H3.3, respectively, and one important difference between histone variant H3.3 and "classical" histone H3.1 or H3.2 is that the 31 st residue at the amino terminus is serine (Ser or S) and H3.1/2 is alanine (Ala or a).
In one embodiment of the invention, the H3K36ac is h3.2k36ac.
In one embodiment of the invention, the inhibitor that inhibits H3K36ac acetylation comprises CPTH2 (CPTH 2 is a potent histone acetyl transferase inhibitor, selectively inhibiting acetylation of histone H3 by Gcn 5), DC-G16, and/or butyrolactone.
In one embodiment of the invention, the inhibitor that inhibits H3K36ac acetylation is CPTH2.
In one embodiment of the invention, the obesity-related disorder comprises obesity-induced metabolic syndrome.
In one embodiment of the invention, the medicament contains an inhibitor that inhibits H3K36ac acetylation, a pharmaceutical carrier, and/or a pharmaceutical adjuvant.
In one embodiment of the invention, the pharmaceutical carrier comprises microcapsules, microspheres, nanoparticles and/or liposomes.
In one embodiment of the invention, the pharmaceutical excipients comprise solvents, propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure modifiers, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-binding agents, integration agents, permeation promoters, pH modifiers, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and/or release retarders.
In one embodiment of the invention, the medicament is in the form of a powder, tablet, granule, capsule, solution, emulsion, suspension or injection.
The invention also provides a molecular marker for assessing obesity phenotype, the molecular marker comprising a level of H3K36ac acetylation.
In one embodiment of the invention, the molecular marker is the level of H3K36ac acetylation.
In one embodiment of the invention, the obese phenotype comprises body weight, body fat rate and/or adipocyte volume. The level of H3K36ac acetylation is up-regulated, the obese phenotype includes a heavy increase, an elevated body fat rate, and fat cell hypertrophy, the level of H3K36ac acetylation is down-regulated, and the obese phenotype includes a heavy decrease, a reduced body fat rate, and a reduced fat cell.
The invention also provides application of the reagent for detecting the molecular marker in the sample to be detected in preparation of products for assessing obesity phenotypes.
In one embodiment of the invention, the obese phenotype comprises body weight, body fat rate and/or adipocyte volume.
In one embodiment of the invention, the product comprises a detection kit.
The invention also provides a diagnostic kit for assessing obese phenotypes, comprising reagents for detecting the above molecular markers in a test sample.
The technical scheme of the invention has the following advantages:
1. the present invention provides a molecular marker for assessing obesity phenotypes, said molecular marker comprising the level of H3K36ac acetylation. Research shows that the dynamic change relation exists between the H3K36ac modification level in white adipose tissue and dietary obesity and lifestyle intervention, and the dynamic change relation is specifically expressed as follows: the H3K36ac level in adipose tissue of the high-fat diet induced mice is obviously increased compared with normal diet mice, the mice have the phenotypes of weight increase, body fat rate increase, fat cell hypertrophy and the like, while the H3K36ac level in adipose tissue of the lifestyle-intervention mice is obviously reduced compared with the high-fat diet induced mice, and the mice have the phenotypes of weight reduction, body fat rate reduction, fat cell volume reduction and the like, so that the H3K36ac acetylation level can be used as a molecular marker for assessing the obesity phenotype, and the method has great application prospect in preparing products for assessing the obesity phenotype.
2. The invention provides an application of an inhibitor for inhibiting H3K36ac acetylation in preparing a medicament for preventing and/or treating obesity and/or obesity-related diseases. Research shows that the inhibitor for inhibiting the acetylation level of H3K36ac has the effects of reducing lipid accumulation and up-regulating the level of lipid metabolism gene PPAR mRNA, so that the acetylation level of H3K36ac can be used as a new target for preventing and treating obesity, and the inhibitor for inhibiting the acetylation of H3K36ac has great application prospect in preparing medicines for preventing and/or treating obesity and/or obesity related diseases.
Drawings
Fig. 1: body weight change in three groups of mice.
Fig. 2: three groups of mice at the end of the experiment were given weight.
Fig. 3: body fat rate status of three groups of mice at the end of the experiment.
Fig. 4: h & E staining results of adipose tissue pathology sections of three groups of mice at the end of the experiment.
Fig. 5: mass spectrometry results for histone H3.2 peptide fragment.
Fig. 6: immunohistochemical staining results of adipose tissue sections of three groups of mice. In fig. 6, a is the H3K36ac immunohistochemical staining result of adipose tissue, and B is the quantitative analysis of the staining result.
Fig. 7: western Blot validation results for histones in three groups of cells.
Fig. 8: results of oil red staining of the three groups of cells.
Fig. 9: mRNA levels of the lipid metabolism gene pparγ in three groups of cells.
Detailed Description
The following experimental examples are provided for better understanding of the present invention, and are not limited to the preferred embodiments, but are not limited to the contents and the protection scope of the present invention, and any product which is the same as or similar to the present invention and obtained by combining the present invention with other features of the prior art under the teaching of the present invention falls within the protection scope of the present invention.
The following examples are not intended to identify specific experimental procedures or conditions, and may be conducted in accordance with the procedures or conditions of conventional experimental procedures described in the literature in the field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.
Experimental example 1
1. Experimental method
To find important acetylation modification sites involved in regulation of obesity, the present study used 8-week-old male c57BL/6J mice (purchased from Vetong Lihua corporation) to construct a diet obese mouse model (8-week-old male c57BL/6J mice induced with a high-fat diet (D12942, research diet) containing 60% kcal fat for 12 weeks) and a lifestyle-intervention weight-loss mouse model (8-week-old male c57BL/6J mice induced with a high-fat diet containing 60% kcal fat for 8 weeks, then changed to normal diet and exercise-intervention for 4 weeks at the same time, exercise regimen was that the treadmill had an aerobic exercise for 14m/min for 1 week +16m/min for 5 weeks of incline for 5 days each time, and a control group was 8-week-old male c57BL/6J mice on a normal diet (mouse SPF-grade normal diet, vetong Lihua) for 12 weeks).
Body weight of three groups of mice was measured weekly from the beginning to the end of feeding, body fat analysis and measurement were performed on the three groups of mice at the end of feeding, after body fat analysis and measurement, adipose tissues of the three groups of mice were fixed and wax blocks were prepared, H & E staining of pathological sections was performed by an automatic staining machine (Leica ST 5010), and photographs of the results were retained.
Taking three groups of mouse adipose tissues, extracting adipose tissue histones, performing proteomics analysis and proteomics acetylation modification histology analysis on peptide fragments by using a high performance liquid chromatography-mass spectrometry tandem analysis method after the adipose tissue histones are digested into peptide fragments by pancreatin, establishing a library, identifying histone difference acetylation modification sites and performing enrichment analysis. The mass spectrometer adopted by the high performance liquid chromatography-mass spectrometry tandem analysis method is timsTOF Pro (Bruker Daltonics), and the library construction analysis adopts proteomic search analysis software Max Quant (v.1.6.15.0).
Three groups of mouse fat wax blocks are taken for slicing and performing immune group analysis on the expression level of H3K36ac, an immune group primary antibody adopts an H3K36ac antibody (PTM Bio), a secondary antibody adopts a rabbit antibody (ZSBB-BIO), DAB is adopted for dyeing, hematoxylin is adopted for back dyeing, and then a slice photo is acquired.
2. Experimental results
The body weight change from the start to the end of the feeding of the three groups of mice is shown in figure 1, the body weight difference of the three groups of mice at the end of the experiment is shown in figure 2, and the body fat rate results of the three groups of mice are shown in figure 3, wherein the body weight of the mice in the control group rises but the rising amplitude is not obvious from the start to the end of the experiment, and the body weight and the body fat rate of the mice in the control group are 31.92 +/-0.93 g and 17.2+/-1.11 g respectively at the end of the experiment; the body weight of the obese mice (i.e. the eating obese mice model) continuously rises and the rising amplitude is obvious from the beginning to the end of the experiment, and at the end of the experiment, the body weight and body fat rate of the obese mice respectively reach 41.61 +/-5.41 g and 32.64+/-3.76 percent which are obviously higher than those of the control group (P < 0.001); from the beginning to the end of the experiment, the body weight of the mice in the intervention group (i.e. the weight-loss mouse model of lifestyle intervention) was continuously increased and then continuously decreased, and at the end of the experiment, the body weight and body fat rate of the mice in the intervention group reached 28.48+ -0.37 g and 18.20+ -3.11%, respectively, which were significantly lower than those in the obese group (P < 0.01).
The H & E staining results of adipose tissue pathology are shown in fig. 4, wherein the fat cell volume of the obese mice (i.e., the eating obese mice model) is significantly increased, the fat drop fusion is increased to squeeze the cell nucleus to one side, the number of fat cells under the same vision is significantly reduced, and the volume of the fat cells of the mice after life style stem prognosis is restored.
The mass spectrum result of the peptide fragment of the histone H3.2 is shown in figure 5, and the figure 5 shows a mass spectrum peak diagram of the peptide fragment near 36 th site of the covered histone H3.2 in the mass spectrum result, which reflects the acetylation modification at 36 th site in the histone H3.2 sequence.
The results of immunohistochemical staining of adipose tissue sections of three groups of mice are shown in FIG. 6 (A is the IHC staining result of adipose tissue sections of different groups of mice, the dark brown region is the region combined with H3K36ac, namely the positive region, the light color is the negative region, and the area of the positive region deeply stained therein is quantified by B), wherein the level of histone H3K36ac in adipose tissue of obese mice (namely the eating obese mouse model) is significantly higher than that of control group (P < 0.001), and the level of histone H3K36ac in adipose tissue of intervening mice (namely the weight-reduced mouse model with lifestyle intervention) is significantly lower than that of obese mice (P < 0.001).
The results show that the H3K36ac level in adipose tissue of a high-fat diet-induced mouse is obviously increased compared with that of a normal diet mouse, the mice have phenotypes such as weight increase, body fat rate increase, fat cell hypertrophy and the like, the H3K36ac level in adipose tissue of a lifestyle-mediated mouse is obviously reduced compared with that of a high-fat diet-induced mouse, and the mice have phenotypes such as weight reduction, body fat rate reduction, fat cell volume reduction and the like, so that the H3K36ac acetylation level can be used as a molecular marker for assessing the obesity phenotype, has great application prospect in preparing products for assessing the obesity phenotype, and can be used as a novel target for potential obesity prevention and treatment for further research.
Experimental example 2
1. Experimental method
To investigate the effect of H3K36ac levels on obesity, the present study established a fat cell model of the high lipid environment and interfered with the inhibitor CPTH2 that inhibits H3K36ac acetylation. Fat cell model of high fat environment is molded by using 3T3-L1 cells (purchased from synergetic cell bank), and the molding is finished after oleic acid intervention for 24 hours after lipid induction (oleic acid treatment simulates high fat diet environment). Cell culture conditions were 5% (v/v) CO 2 Cell culture was performed using DMEM medium (available from Gibco) containing 10% (v/v) fetal bovine serum (FBS, available from Gibco) as a complete medium in an incubator at 37 ℃. The molding process uses a cocktail method commonly used in the academy (see the literature "Ruiz-Obeda FJ, rupurez AI, gomez-Llorente C, gil A, aguilera CM. Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A review, int J Mol Sci 2016 Jun 30;17 (7): 1040)") for lipid induction, and the reagents used for lipid induction are bovine insulin, IBMX, and dexamethasone.
The specific experimental process is as follows: 3T3-L1 cells were plated at 0.3X10 per well 6 After plating the inoculum size of each cell to a cell density of 90% or more in a 6-well plate added with complete medium, observing whether or not the cells are in contact inhibition, starting lipogenesis induction after 2 days of the contact inhibition of the cells, wherein the first stage of lipogenesis induction adopts complete medium induction culture with bovine insulin (1. Mu.M, solarbio), IBMX (0.5. Mu.M, sigma) and dexamethasone (1. Mu.M, sigma) for 2 days, and the second stage of lipogenesis induction adopts complete medium induction culture with bovine insulin (1. Mu.M, solarbio) for 4 days. After the end of adipogenic induction, the cells were divided into experimental groups,An intervention group and a control group, wherein the experimental group cells were incubated with complete medium supplemented with oleic acid (500 mM, MCE, HY-N1446B) for 24 hours after lipid formation induction, the intervention group cells were incubated with complete medium supplemented with H3K36ac inhibitor CPTH2 (10 mM, MCE) for 1 hour after lipid formation induction, and then with complete medium supplemented with oleic acid (500 mM, MCE, HY-N1446B) for 24 hours, and the control group cells were incubated with complete medium containing 20% (w/v, g/100 mL) bovine serum albumin after lipid formation induction for 24 hours. The addition of complete medium in 6-well plates during cell culture and incubation was 2mL per well.
After the incubation, the histones of the three groups of cells were extracted using a kit (epiqueik) and stored at-20 ℃ for later use. Western Blotting was performed using 15% (w/v, g/100 mL) gel, electrophoresed, electroblotted, milk blocked, incubated with antibody, primary antibody with H3K36ac antibody (PTM Bio), and secondary antibody with rabbit antibody (ZSBC-BIO), and developed to verify H3K36ac levels in the three groups of cells. Performing oil red staining on the three groups of cells; the oil red dyeing is as follows: taking out the cells in the 6-well plate subjected to the intervention, fixing by 4% (w/v, g/100 mL) paraformaldehyde, dehydrating by 100% (v/v) isopropanol, incubating for 30min at 37 ℃ by using oil red dye liquor (purchased from Cunninghamia sinensis Bridger Corp., beijing), dehydrating by using 80% (v/v) isopropanol, eluting by using pure water twice, and finally collecting photographs after oil red staining under a mirror, wherein the addition amount of the reagent used for oil red staining in the 6-well plate is 1mL per well. After extracting RNA in three groups of cells using a kit (QIAGEN), reverse transcription is performed using a reverse transcription kit (Abm), and mRNA obtained by reverse transcription is subjected to rt-qPCR to detect the mRNA level of a lipid metabolism gene PPARgamma in the three groups of cells; the rt-qPCR system (10. Mu.L) was: 0.3. Mu.L of primer F (shown as SEQ ID NO.1, concentration of 10. Mu.M), 0.3. Mu.L of primer R (shown as SEQ ID NO.2, concentration of 10. Mu.M), 5. Mu.L of qPCR masterMix (G891, abm), 4.4. Mu.L of cDNA; the amplification procedure for rt-qPCR was: keeping at 50 ℃ for 2min and at 95 ℃ for 10min; 15s at 95℃and 30s at 60℃for 40 cycles; 15s at 95℃and 30s at 60℃and 15s at 95 ℃.
2. Experimental results
The results of Western Blot verification of H3K36ac levels in the three groups of cells are shown in FIG. 7, where the H3K36ac levels in the intervening group of cells were lower than in the experimental group, indicating that CPTH2 inhibited H3K36ac expression.
The results of oil red staining of the three groups of cells are shown in fig. 8, wherein the lipid accumulation of the cells of the intervening group was lower than that of the experimental group, indicating that lipid accumulation of adipocytes was decreased after inhibiting H3K36ac expression.
The mRNA levels of the lipid metabolism gene PPAR in the three groups of cells are shown in fig. 9, wherein the mRNA levels of the lipid metabolism gene PPAR in the intervening group of cells are higher than those in the experimental group, and the result shows that the mRNA levels of the lipid metabolism gene PPAR are up-regulated after inhibiting the expression of H3K36 ac.
The results show that the inhibition of the acetylation level of H3K36ac has the effects of reducing lipid accumulation and up-regulating the level of lipid metabolism gene PPAR mRNA, and the acetylation level of H3K36ac can be used as a novel target for preventing and treating obesity, and the inhibitor for inhibiting the acetylation of H3K36ac has great application prospect in preparing medicines for preventing and/or treating obesity and/or obesity-related diseases.
It should be apparent that the above experimental examples are given for clarity of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (10)
1. Use of an inhibitor that inhibits H3K36ac acetylation in the manufacture of a medicament for the prevention and/or treatment of obesity and/or obesity-related disorders.
2. The use according to claim 1, wherein the H3K36ac comprises h3.1k36ac, h3.2k36ac and/or h3.3k36ac.
3. The use according to claim 1, wherein the inhibitor of H3K36ac acetylation comprises CPTH2, DC-G16 and/or butyrolactone.
4. The use according to claim 1, wherein the obesity-related disorder comprises obesity-induced metabolic syndrome.
5. The use according to any one of claims 1 to 3, wherein the medicament comprises an inhibitor for inhibiting H3K36ac acetylation, a pharmaceutical carrier and/or a pharmaceutical adjuvant.
6. The use according to claim 5, wherein the pharmaceutical carrier comprises microcapsules, microspheres, nanoparticles and/or liposomes; the pharmaceutical excipients comprise solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, permeation promoters, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids and/or release retarders.
7. A molecular marker for assessing obesity phenotype, wherein the molecular marker comprises H3K36ac acetylation level.
8. The molecular marker of claim 7, wherein the obese phenotype comprises body weight, body fat rate, and/or adipocyte volume.
9. Use of a reagent for detecting a molecular marker according to claim 7 or 8 in a sample to be tested for the preparation of a product for assessing the obese phenotype.
10. A diagnostic kit for assessing obese phenotypes, comprising reagents for detecting the molecular markers of claim 7 or 8 in a test sample.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410160071.1A CN117695395A (en) | 2024-02-04 | 2024-02-04 | Application of H3K36ac inhibitor in preparation of medicine for treating obesity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410160071.1A CN117695395A (en) | 2024-02-04 | 2024-02-04 | Application of H3K36ac inhibitor in preparation of medicine for treating obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117695395A true CN117695395A (en) | 2024-03-15 |
Family
ID=90146539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410160071.1A Pending CN117695395A (en) | 2024-02-04 | 2024-02-04 | Application of H3K36ac inhibitor in preparation of medicine for treating obesity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117695395A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011016869A1 (en) * | 2009-08-06 | 2011-02-10 | Kamran Tahamtanzadeh | Methods and compositions for drug discovery |
| JP2014105177A (en) * | 2012-11-27 | 2014-06-09 | National Center For Global Health & Medicine | Pharmaceutical composition for diabetes therapy and screening method of active ingredient thereof |
| CN109414414A (en) * | 2016-03-16 | 2019-03-01 | 戴维·格拉德斯通研究所 | Method and composition for treating obesity and/or diabetes and for identifying candidate therapeutic agent |
| WO2022254465A1 (en) * | 2021-06-02 | 2022-12-08 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | Small molecule modulator targeting a rare histone modification regulating adipogenesis and pharmaceutical formulation thereof |
-
2024
- 2024-02-04 CN CN202410160071.1A patent/CN117695395A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011016869A1 (en) * | 2009-08-06 | 2011-02-10 | Kamran Tahamtanzadeh | Methods and compositions for drug discovery |
| JP2014105177A (en) * | 2012-11-27 | 2014-06-09 | National Center For Global Health & Medicine | Pharmaceutical composition for diabetes therapy and screening method of active ingredient thereof |
| CN109414414A (en) * | 2016-03-16 | 2019-03-01 | 戴维·格拉德斯通研究所 | Method and composition for treating obesity and/or diabetes and for identifying candidate therapeutic agent |
| WO2022254465A1 (en) * | 2021-06-02 | 2022-12-08 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | Small molecule modulator targeting a rare histone modification regulating adipogenesis and pharmaceutical formulation thereof |
Non-Patent Citations (5)
| Title |
|---|
| AQUEA, F等: ""Chemical inhibition of the histone acetyltransferase activity in Arabidopsis thaliana"", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 483, no. 1, 29 January 2017 (2017-01-29), pages 664 - 668 * |
| CHUNG, MY等: ""Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model"", MOLECULAR METABOLISM, vol. 19, 10 November 2018 (2018-11-10), pages 34 - 48 * |
| LEE, J等: ""3, 4-dihydroxytoluene, a metabolite of rutin, suppresses the progression of nonalcoholic fatty liver disease in mice by inhibiting p300 histone acetyltransferase activity"", ACTA PHARMACOLOGICA SINICA, vol. 42, no. 9, 10 December 2020 (2020-12-10), pages 1449 - 1460, XP037543844, DOI: 10.1038/s41401-020-00571-7 * |
| 艾维缔科技怀来有限公司: "总组蛋白H3K36乙酰化定量试剂盒（比色法）", pages 6, Retrieved from the Internet <URL:http://v1/cecdn.yun300.cn/100001_2004305221/A-P-4018-总组蛋白H3K36乙酰化定量试剂盒（比色法）.pdf> * |
| 韩杰: "靶向乙酰转移酶和去泛素化酶小分子抑制剂的发现与机制研究", 《医药卫生科技辑》, 15 July 2020 (2020-07-15), pages 079 - 5 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | SCARNA10, a nuclear-retained long non-coding RNA, promotes liver fibrosis and serves as a potential biomarker | |
| Fan et al. | Effect of lncRNA MALAT1 on rats with myocardial infarction through regulating ERK/MAPK signaling pathway. | |
| Bai et al. | CircRNA 010567 improves myocardial infarction rats through inhibiting TGF-β1. | |
| CN112961913B (en) | Application of lncRNA in diagnosis and treatment of recurrent abortion | |
| Chao et al. | miR-429-3p/LPIN1 axis promotes chicken abdominal fat deposition via PPARγ pathway | |
| Zhong et al. | LNK deficiency decreases obesity-induced insulin resistance by regulating GLUT4 through the PI3K-Akt-AS160 pathway in adipose tissue | |
| Zhu et al. | The S100 calcium binding protein A11 promotes liver fibrogenesis by targeting TGF-β signaling | |
| CN112195244B (en) | Application of GMFB (GMFB) as hepatocyte liver cancer biomarker | |
| Okada et al. | Autocrine pathways involving S100A8 and/or S100A9 that are postulated to regulate the immunological functions of macrophages in rats | |
| CN111850113A (en) | Application of S100A11 gene and protein as non-alcoholic fatty liver biomarker and therapeutic target | |
| CN117695395A (en) | Application of H3K36ac inhibitor in preparation of medicine for treating obesity | |
| CN109097358B (en) | Application of lncRNA in prevention or treatment of hypertension | |
| CN112680512B (en) | Application of circular RNA biomarker circ-Glis3 | |
| Li et al. | miR-582-5p targets Skp1 and regulates NF-κB signaling-mediated inflammation | |
| Wang et al. | MicroRNA-124 expression in Kupffer cells modulates liver injury by targeting IL-6/STAT3 signaling | |
| CN113293208B (en) | Molecular marker related to lung cancer proliferation and metastasis and application thereof | |
| Zhu et al. | Inhibition of lncRNA NFIA-AS1 alleviates abnormal proliferation and inflammation of vascular smooth muscle cells in atherosclerosis by regulating miR-125a-3p/AKT1 axis | |
| CN114438199B (en) | Application of BBOX1-AS1 AS recurrent abortion diagnosis marker and therapeutic target | |
| CN111154863A (en) | Application of lncRNA in preparation of product for diagnosing and/or treating osteoarthritis | |
| CN116492463B (en) | Application of CD155 molecules in liver fibrosis field | |
| CN110305962A (en) | DKC1 and application of the HIF-1 α in synergistic treatment colorectal cancer | |
| TW200405006A (en) | Treatment of liver diseases | |
| CN114107492B (en) | Molecular marker for tumor molecular typing and therapeutic drug evaluation, and detection primer and kit thereof | |
| WO2023202223A1 (en) | Reagent for treating neuroendocrine prostate cancer and use thereof | |
| US20070065850A1 (en) | Method for diagnosis of heart failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |