| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T65200 | ||||
| Target Name | Corticosteroid 11-beta-dehydrogenase, isozyme 1 | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | 2-(adamantan-1-ylamino)-5,5-diethyl-oxazol-4-one | Drug Info | Ki = 4 nM | [528929] | |
| 2-(benzylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | Ki = 1761 nM | [528929] | ||
| BVT.2733 | Drug Info | IC50 = 52 nM | [530715] | ||
| 3-acetyl-11-keto-ursolic acid | Drug Info | IC50 = 1350 nM | [530656] | ||
| GLYCYRRHIZIN | Drug Info | IC50 = 8 nM | [530241] | ||
| URSOLIC ACID | Drug Info | IC50 = 1900 nM | [530656] | ||
| 3-epicorosolic acid methyl ester | Drug Info | IC50 = 5200 nM | [530656] | ||
| 1-(4-fluorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 90 nM | [528829] | ||
| 1,1-diphenyl-3-(phenylsulfonyl)propan-2-one | Drug Info | IC50 = 2900 nM | [528829] | ||
| 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 1310 nM | [528829] | ||
| Adamantan-1-yl-(4-ethyl-piperazin-1-yl)-methanone | Drug Info | IC50 = 300 nM | [528722] | ||
| 1-(4-chlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 200 nM | [528829] | ||
| Adamantan-1-yl-piperidin-1-yl-methanone | Drug Info | IC50 = 134 nM | [528722] | ||
| 1-(3-methylpyridin-2-yl)-4-tosylpiperazine | Drug Info | IC50 = 240 nM | [529500] | ||
| (4-methoxyphenyl)(4-phenylazepan-1-yl)methanone | Drug Info | IC50 = 9 nM | [530270] | ||
| Adamantan-1-yl-piperazin-1-yl-methanone | Drug Info | IC50 = 8200 nM | [528722] | ||
| 2-(phenylsulfonyl)-1-(thiophen-3-yl)ethanone | Drug Info | IC50 = 345 nM | [528829] | ||
| 1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 75 nM | [528829] | ||
| 1-(3,4-dichlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 101 nM | [528829] | ||
| 1-(3,5-dimethylphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 1200 nM | [528829] | ||
| 1-(4-tert-butylphenylsulfonyl)-4-methoxyazepane | Drug Info | IC50 = 165 nM | [530270] | ||
| 1-(phenylsulfonyl)butan-2-one | Drug Info | IC50 = 15000 nM | [528829] | ||
| 1-phenyl-3-(phenylsulfonyl)propan-1-one | Drug Info | IC50 = 17400 nM | [528829] | ||
| 1-(4-ethylphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | IC50 = 1406 nM | [530270] | ||
| 5,5-diethyl-2-(phenethylamino)oxazol-4(5H)-one | Drug Info | Ki = 6451 nM | [528929] | ||
| N-benzyl-N-(phenylsulfonyl)benzamide | Drug Info | IC50 = 5700 nM | [528829] | ||
| Piperidine-1-carboxylic acid adamantan-2-yl ester | Drug Info | IC50 = 53 nM | [531176] | ||
| 1-(3-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | IC50 = 60 nM | [528829] | ||
| 1-(4-fluorophenyl)-3-(phenylsulfonyl)propan-1-one | Drug Info | IC50 = 19600 nM | [528829] | ||
| 2-(phenylsulfonyl)-1-p-tolylethanone | Drug Info | IC50 = 102 nM | [528829] | ||
| 2-(2-chlorophenylamino)-5-methylthiazol-4(5H)-one | Drug Info | Ki = 350 nM | [529083] | ||
| 5-isopropyl-2-(phenylamino)thiazol-4(5H)-one | Drug Info | IC50 = 310 nM | [529083] | ||
| Adamantan-1-yl-pyrrolidin-1-yl-methanone | Drug Info | IC50 = 498 nM | [528722] | ||
| 1-phenyl-2-(1-phenyl-1H-tetrazol-5-yloxy)ethanone | Drug Info | IC50 = 971 nM | [530901] | ||
| MERCK-544 | Drug Info | IC50 = 97 nM | [530715] | ||
| 1-phenyl-4-(1-phenyl-1H-tetrazol-5-yl)butan-2-one | Drug Info | IC50 = 820 nM | [530901] | ||
| 1-(1-phenyl-1H-tetrazol-5-ylthio)propan-2-one | Drug Info | IC50 = 14500 nM | [530901] | ||
| 2-(cyclooctylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | Ki = 10 nM | [528929] | ||
| 1-(4-tert-butylphenylsulfonyl)azepan-4-ol | Drug Info | IC50 = 629 nM | [530270] | ||
| AMG-221 | Drug Info | IC50 = 10.1 nM | [530911] | ||
| FIG 1 | Drug Info | IC50 = 109 nM | [529441] | ||
| 1-(4-ethylpiperazin-1-yl)-2-phenylethanone | Drug Info | IC50 = 7200 nM | [528722] | ||
| Adamantan-2-yl-piperidin-1-yl-methanone | Drug Info | IC50 = 200 nM | [528722] | ||
| 1-(3-nitropyridin-2-yl)-4-tosylpiperazine | Drug Info | IC50 = 291 nM | [529500] | ||
| 11-keto-ursolic acid | Drug Info | IC50 = 2060 nM | [530656] | ||
| Corosolic acid | Drug Info | IC50 = 810 nM | [530656] | ||
| PF-877423 | Drug Info | IC50 = 4.15 nM | [530826] | ||
| 1-(4-methoxyphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | IC50 = 1981 nM | [530270] | ||
| 1-(4-chlorophenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | IC50 = 2721 nM | [530270] | ||
| Piperidine-1-carboxylic acid adamantan-2-ylamide | Drug Info | IC50 = 32 nM | [531176] | ||
| 1-(3-chloropyridin-2-yl)-4-tosylpiperazine | Drug Info | IC50 = 146 nM | [529500] | ||
| GLYCYRRHIZIN | Drug Info | IC50 = 15 nM | [530246] | ||
| Tormentic acid methyl ester | Drug Info | IC50 = 9400 nM | [530656] | ||
| 2-(o-toluidino)-5-isopropylthiazol-4(5H)-one | Drug Info | IC50 = 1.3 nM | [529083] | ||
| PF-915275 | Drug Info | Ki = 750 nM | [530170] | ||
| 1-(2-adamantyl)-3-benzylpyrrolidin-2-one | Drug Info | IC50 = 64 nM | [528391] | ||
| 3-benzyl-1-cyclohexylpyrrolidin-2-one | Drug Info | IC50 = 107 nM | [528391] | ||
| 2-(o-toluidino)-5-ethylthiazol-4(5H)-one | Drug Info | Ki = 189 nM | [529430] | ||
| INCB13739 | Drug Info | IC50 = 3~70 nM | |||
| 2-(4-tosylpiperazin-1-yl)nicotinonitrile | Drug Info | IC50 = 628 nM | [529500] | ||
| Action against Disease Model | BVT.2733 | BVT.2733 has an IC50 of 96 nM for mouse 11 beta-HSD1. | [552885] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Obese h uMans and rodents show increased 11beta-HSD1 in adipose tissue. Transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue faithfully recapitulate metabolic syndrome. Conversely, 11beta-HSD1 knockout mice have a 'cardioprotective' phenotype, whose effects are also seen with 11beta-HSD1 inhibitors in rodents. However, any major metabolic effects of 11beta-HSD1 inhibition in h uMans are, as yet, unreported. 11beta-HSD1 null mice also resist cognitive decline with ageing, and this is seen in h uMans with a prototypic inhibitor. Thus 11beta-HSD1 inhibition is an emerging pleiotropic therapeutic target. | [552885] | |||
| References | |||||
| Ref 552885 | Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83. doi: 10.1158/1078-0432.CCR-08-0652. | ||||
| Ref 528929 | Bioorg Med Chem Lett. 2007 Sep 1;17(17):4837-40. Epub 2007 Jun 20.Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. | ||||
| Ref 528929 | Bioorg Med Chem Lett. 2007 Sep 1;17(17):4837-40. Epub 2007 Jun 20.Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. | ||||
| Ref 530715 | Bioorg Med Chem Lett. 2010 Mar 1;20(5):1551-4. Epub 2010 Jan 25.Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 530241 | Bioorg Med Chem Lett. 2009 Aug 1;19(15):4455-8. Epub 2009 May 15.4-(Phenylsulfonamidomethyl)benzamides as potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1 with efficacy in diabetic ob/ob mice. | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 529500 | Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. Epub 2008 May 10.Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 528929 | Bioorg Med Chem Lett. 2007 Sep 1;17(17):4837-40. Epub 2007 Jun 20.Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 531176 | Bioorg Med Chem Lett. 2010 Nov 15;20(22):6725-9. Epub 2010 Sep 7.Discovery and optimization of adamantyl carbamate inhibitors of 11|A-HSD1. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 528829 | Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. Epub 2007 Apr 25.beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. | ||||
| Ref 529083 | Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25.The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors. | ||||
| Ref 529083 | Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25.The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 530901 | Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. Epub 2010 Apr 18.Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles. | ||||
| Ref 530715 | Bioorg Med Chem Lett. 2010 Mar 1;20(5):1551-4. Epub 2010 Jan 25.Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 530901 | Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. Epub 2010 Apr 18.Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles. | ||||
| Ref 530901 | Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. Epub 2010 Apr 18.Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles. | ||||
| Ref 528929 | Bioorg Med Chem Lett. 2007 Sep 1;17(17):4837-40. Epub 2007 Jun 20.Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 530911 | J Med Chem. 2010 Jun 10;53(11):4481-7.Discovery of a potent, orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). | ||||
| Ref 529441 | Bioorg Med Chem Lett. 2008 Jun 1;18(11):3405-11. Epub 2008 Apr 10.4-Methyl-5-phenyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 528722 | Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. Epub 2007 Feb 25.Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. | ||||
| Ref 529500 | Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. Epub 2008 May 10.Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 530826 | Bioorg Med Chem Lett. 2010 May 1;20(9):2897-902. Epub 2010 Mar 10.The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors. | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 530270 | Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. Epub 2009 Jul 8.The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
| Ref 531176 | Bioorg Med Chem Lett. 2010 Nov 15;20(22):6725-9. Epub 2010 Sep 7.Discovery and optimization of adamantyl carbamate inhibitors of 11|A-HSD1. | ||||
| Ref 529500 | Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. Epub 2008 May 10.Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). | ||||
| Ref 530246 | Bioorg Med Chem. 2009 Aug 1;17(15):5722-32. Epub 2009 Jun 12.Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. | ||||
| Ref 530656 | Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. Epub 2010 Jan 11.11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. | ||||
| Ref 529083 | Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25.The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors. | ||||
| Ref 530170 | Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. Epub 2009 May 7.N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275. | ||||
| Ref 528391 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5555-60. Epub 2006 Aug 23.Discovery of orally active butyrolactam 11beta-HSD1 inhibitors. | ||||
| Ref 528391 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5555-60. Epub 2006 Aug 23.Discovery of orally active butyrolactam 11beta-HSD1 inhibitors. | ||||
| Ref 529430 | J Med Chem. 2008 May 22;51(10):2933-43. Epub 2008 Apr 18.2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice. | ||||
| Ref 529500 | Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. Epub 2008 May 10.Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). | ||||
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