RU2007117771A - E2-epf5-новый терапевтический белок и мишень - Google Patents
E2-epf5-новый терапевтический белок и мишень Download PDFInfo
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- RU2007117771A RU2007117771A RU2007117771/14A RU2007117771A RU2007117771A RU 2007117771 A RU2007117771 A RU 2007117771A RU 2007117771/14 A RU2007117771/14 A RU 2007117771/14A RU 2007117771 A RU2007117771 A RU 2007117771A RU 2007117771 A RU2007117771 A RU 2007117771A
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- epf5
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- angiogenesis
- conjugating enzyme
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- 108090000623 proteins and genes Proteins 0.000 title claims 7
- 230000001225 therapeutic effect Effects 0.000 title claims 2
- 102000004169 proteins and genes Human genes 0.000 title 1
- 238000000034 method Methods 0.000 claims 16
- 230000002401 inhibitory effect Effects 0.000 claims 9
- 230000033115 angiogenesis Effects 0.000 claims 8
- 102100028718 Ubiquitin-conjugating enzyme E2 S Human genes 0.000 claims 7
- 101710192900 Ubiquitin-conjugating enzyme E2 S Proteins 0.000 claims 7
- 150000001875 compounds Chemical class 0.000 claims 7
- 206010029113 Neovascularisation Diseases 0.000 claims 6
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- 239000003795 chemical substances by application Substances 0.000 claims 4
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- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
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- 108700012439 CA9 Proteins 0.000 claims 2
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 claims 2
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- 108090000848 Ubiquitin Proteins 0.000 claims 2
- 102000044159 Ubiquitin Human genes 0.000 claims 2
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- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 claims 1
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
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- 101001048456 Homo sapiens Protein Hook homolog 2 Proteins 0.000 claims 1
- 102100023426 Kinesin-like protein KIF2A Human genes 0.000 claims 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims 1
- 101150038998 PLAUR gene Proteins 0.000 claims 1
- 108091006296 SLC2A1 Proteins 0.000 claims 1
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- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 claims 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 claims 1
- 108060008747 Ubiquitin-Conjugating Enzyme Proteins 0.000 claims 1
- 102000003431 Ubiquitin-Conjugating Enzyme Human genes 0.000 claims 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims 1
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- 210000002966 serum Anatomy 0.000 claims 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims 1
- 229940126585 therapeutic drug Drugs 0.000 claims 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
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- C12Y603/02—Acid—amino-acid ligases (peptide synthases)(6.3.2)
- C12Y603/02019—Ubiquitin-protein ligase (6.3.2.19), i.e. ubiquitin-conjugating enzyme
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Claims (19)
1. Способ лечения заболевания, связанного с аберрантной
неоваскуляризациеи, заключающийся во введении эффективного количества агента, ингибирующего экспрессию гена, кодирующего убиквитин-конъюгирующий фермент E2-EPF5 или ингибирующего активность продукта гена E2-EPF5.
2. Способ по п.1, в котором аберрантная неоваскуляризация представляет собой VEGF-зависимую васкуляризацию.
3. Способ по п.1, в котором VEGF-зависимая васкуляризация представляет собой ангиогенез в опухолях, синовиальный ангиогенез при ревматоидном артрите, глазную неоваскуляризацию, которую наблюдают при диабетической ретинопатии, кожный ангиогенез при псориазе или ангиогенез, индуцированный гипоксией, при циррозе печени.
4. Способ по п.1, в котором указанный агент представляет собой ингибирующую нуклеиновую кислоту, способную к специфическому ингибированию убиквитин-конъюгирующего фермента E2-EPF5.
5. Способ по п.4, в котором указанная ингибирующая нуклеиновая кислота представляет собой антисмысловой олигонуклеотид или siPHK.
6. Способ по п.1, в котором указанный агент представляет собой антитело, специфически связывающееся с убиквитин-конъюгирующим ферментом E2-EPF5.
7. Фармацевтическая композиция, включающая эффективное количество агента, ингибирующего экспрессию гена, кодирующего убиквитин-конъюгирующий фермент E2-EPF5, или ингибирующего активность продукта гена E2-EPF5, и фармацевтически приемлемый носитель.
8. Фармацевтическая композиция по п.7, в которой ингибитор E2-EPF5 представляет собой антисмысловой олигонуклеотид или siPHK.
9. Фармацевтическая композиция по п.8, в которой ингибитор E2-EPF5 представляет собой антитело, специфически связывающее убиквитин-конъюгирующий фермент E2-EPF5.
10. Способ идентификации соединения, используемого для ингибирования аберрантной неоваскуляризации, заключающийся в:
(а) контактировании убиквитин-конъюгирующего фермента E2-EPF5 с тестируемым соединением,
(б) детекции модуляции биологической активности убиквитин-конъюгирующего фермента E2-EPF5.
11. Способ идентификации соединения, используемого для лечения
заболевания, связанного с аберрантной неоваскуляризацией, заключающийся в:
i) контактировании тестируемого соединения с убиквитин-конъюгирующим ферментом E2-EPF5 в модельных условиях, допускающих проявление биологической активности E2-EPF5;
ii) определение уровня указанной по меньшей мере одной биологической активности E2-EPF5;
iii) сравнение указанного уровня с уровнем в контрольном образце, в котором отсутствует указанное тестируемое соединение, и, необязательно,
iv) отбор тестируемого соединения, которое вызывает изменение указанного уровня, для дальнейшего тестирования в качестве потенциального терапевтического препарата для профилактического и/или терапевтического лечения заболевания, связанного с нарушенной регуляцией уровня глюкозы в сыворотке или нарушением обмена веществ.
12. Способ по п.10, в котором биологическая активность E2-EPF5 понижена.
13. Способ по п.12, в котором аберрантная васкуляризация представляет собой ангиогенез в опухолях, синовиальный ангиогенез при ревматоидном артрите, глазную неоваскуляризацию, как наблюдают при диабетической ретинопатии, кожный ангиогенез при псориазе или ангиогенез, индуцированный гипоксией, при циррозе печени.
14. Соединение, идентифицированное способом по п.10-13.
15. Способ ингибирования регулируемой HIF-1 экспрессии, заключающийся в ингибировании экспрессии фермента E2-EPF5, связанного с конъюгированием убиквитина.
16. Способ по п.15, в котором указанный HIF-1-регулируемый ген выбран из группы, состоящей из GLUT-1, GLUT-3, HK2, ЕРО, NOS2, VEGF, TGF-α, TGF-β, VEGFR-2, C-Met, UPAR, CXCR4, углеродангидразы IX (CAIX).
17. Способ по п.15, в котором указанный HIF-1-регулируемый ген представляет собой VEGF.
18. Способ ингибирования ангиогенеза опухоли, заключающийся в ингибировании экспрессии фермента E2-EPF5, связанного с конъюгированием убиквитина.
19. Способ по п.15, в котором указанное ингибирование осуществляют посредством ингибирующей нуклеиновой кислоты или антитела.
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| US61890704P | 2004-10-14 | 2004-10-14 | |
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| US9066976B2 (en) | 2005-11-11 | 2015-06-30 | Korea Research Institute Of Bioscience And Biotechnology | Method for therapeutic angiogenesis |
| KR100877824B1 (ko) * | 2005-11-11 | 2009-01-12 | 한국생명공학연구원 | Ｅ2ｅｐｆ ｕｃｐ-ｖｈｌ 상호작용 및 그 용도 |
| CA2771971A1 (en) * | 2006-06-09 | 2007-12-13 | Kabushiki Kaisha Yakult Honsha | Gene involved in immortalization of human cancer cell and use thereof |
| ITMI20101030A1 (it) * | 2010-06-09 | 2011-12-10 | Sergio Capaccioli | Uso di oligonucleotidi antisenso per il trattamento di degenerazioni e neoplasie retiniche |
| CA2921652A1 (en) * | 2013-08-21 | 2015-02-26 | Manuel A. Riquelme | Compositions and methods for targeting connexin hemichannels |
| JP5990308B1 (ja) * | 2015-08-05 | 2016-09-14 | 和英 宮本 | 人工合成疑似ｅ３を有効成分とする、疾患診断を補助する方法および装置、それを用いた疾患診断キットおよびそれを用いた抗癌剤選択支援方法 |
| CN111228502A (zh) * | 2020-03-10 | 2020-06-05 | 新疆医科大学第三附属医院 | 人ube2s基因的用途及相关产品 |
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| US20030232436A1 (en) * | 2002-06-14 | 2003-12-18 | Isis Pharmaceuticals Inc. | Antisense modulation of E2-EPF expression |
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| JP2008516953A (ja) | 2008-05-22 |
| EP1802343A2 (en) | 2007-07-04 |
| KR20070083640A (ko) | 2007-08-24 |
| CA2580883A1 (en) | 2006-04-27 |
| AU2005295863A1 (en) | 2006-04-27 |
| BRPI0518132A (pt) | 2008-10-28 |
| WO2006044366A3 (en) | 2007-01-04 |
| CN101039694A (zh) | 2007-09-19 |
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