Target Information
Target General Infomation | |||||
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Target ID |
T65200
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Former ID |
TTDC00070
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Target Name |
Corticosteroid 11-beta-dehydrogenase, isozyme 1
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Gene Name |
HSD11B1
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Synonyms |
11 beta-hydroxysteroid dehydrogenase type 1; 11-DH; 11-beta-HSD1; 11-beta-hydroxysteroid dehydrogenase 1; 11HSD1; 11beta-HSD1A; 11beta-HSD2; HSD11B1
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Target Type |
Clinical Trial
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Disease | Atherosclerosis [ICD9: 414.0, 440; ICD10: I70] | ||||
Diabetes; Obesity [ICD9: 250, 278; ICD10: E08-E13, E66] | |||||
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1] | |||||
Hypercholesterolemia [ICD10: E78] | |||||
Influenza virus [ICD10: J11.1] | |||||
Lipid metabolism disorder [ICD10: E75-E78] | |||||
Metabolic disorders [ICD9: 270-279; ICD10: E70-E89] | |||||
Metabolic syndrome x [ICD9: 277.7; ICD10: E88.81] | |||||
Non-insulin dependent diabetes [ICD10: E11.9] | |||||
Ocular hypertension [ICD9: 365.04; ICD10: H40.0] | |||||
Type 2 diabetes [ICD9: 250; ICD10: E11] | |||||
Function |
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7- ketocholesterol to 7-beta-hydroxycholesterol (By similarity).
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BioChemical Class |
Short-chain dehydrogenases reductases
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Target Validation |
T65200
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UniProt ID | |||||
EC Number |
EC 1.1.1.146
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Sequence |
MAFMKKYLLPILGLFMAYYYYSANEEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAH
VVVTARSKETLQKVVSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNH ITNTSLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKVAYPMV AAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMKAVSGIVHMQAAPKEE CALEIIKGGALRQEEVYYDSSLWTTLLIRNPCRKILEFLYSTSYNMDRFINK |
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Drugs and Mode of Action | |||||
Drug(s) | GLYCYRRHIZIN | Drug Info | Phase 3 | Influenza virus | [467927], [523449] |
INCB13739 | Drug Info | Phase 2a | Type 2 diabetes | [522347] | |
AZD-4017 | Drug Info | Phase 2 | Ocular hypertension | [523126], [542670] | |
BMS-770767 | Drug Info | Phase 2 | Hypercholesterolemia | [522932] | |
INCB13739 | Drug Info | Phase 2 | Diabetes | [522347] | |
JTT-654 | Drug Info | Phase 2 | Type 2 diabetes | [522824] | |
RG-4929 | Drug Info | Phase 2 | Metabolic disorders | [523728] | |
AZD8329 | Drug Info | Phase 1 | Diabetes; Obesity | [542690], [550290] | |
BI-135585 | Drug Info | Phase 1 | Type 2 diabetes | [523331] | |
BMS-816336 | Drug Info | Phase 1 | Lipid metabolism disorder | [522787] | |
Flavanone | Drug Info | Phase 1 | Discovery agent | [522793], [540674] | |
HPP-851 | Drug Info | Preclinical | Metabolic disorders | [548697] | |
LY-2523199 | Drug Info | Discontinued in Phase 2 | Type 2 diabetes | [549275] | |
AMG-221 | Drug Info | Discontinued in Phase 1 | Metabolic disorders | [547606] | |
PF-915275 | Drug Info | Discontinued in Phase 1 | Non-insulin dependent diabetes | [548447] | |
BVT-3498 | Drug Info | Terminated | Metabolic disorders | [531312] | |
Inhibitor | (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE | Drug Info | [551374] | ||
(4-methoxyphenyl)(4-phenylazepan-1-yl)methanone | Drug Info | [530270] | |||
1,1-diphenyl-3-(phenylsulfonyl)propan-2-one | Drug Info | [528829] | |||
1-(1-phenyl-1H-tetrazol-5-ylthio)propan-2-one | Drug Info | [530901] | |||
1-(2-adamantyl)-3-benzylpyrrolidin-2-one | Drug Info | [528391] | |||
1-(3,4-dichlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(3,5-dimethylphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(3-chloropyridin-2-yl)-4-tosylpiperazine | Drug Info | [529500] | |||
1-(3-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(3-methylpyridin-2-yl)-4-tosylpiperazine | Drug Info | [529500] | |||
1-(3-nitropyridin-2-yl)-4-tosylpiperazine | Drug Info | [529500] | |||
1-(4-chlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(4-chlorophenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [530270] | |||
1-(4-ethylphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [530270] | |||
1-(4-ethylpiperazin-1-yl)-2-phenylethanone | Drug Info | [528722] | |||
1-(4-fluorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(4-fluorophenyl)-3-(phenylsulfonyl)propan-1-one | Drug Info | [528829] | |||
1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(4-methoxyphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [530270] | |||
1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [528829] | |||
1-(4-tert-butylphenylsulfonyl)-4-methoxyazepane | Drug Info | [530270] | |||
1-(4-tert-butylphenylsulfonyl)azepan-4-ol | Drug Info | [530270] | |||
1-(phenylsulfonyl)butan-2-one | Drug Info | [528829] | |||
1-phenyl-2-(1-phenyl-1H-tetrazol-5-yloxy)ethanone | Drug Info | [530901] | |||
1-phenyl-3-(phenylsulfonyl)propan-1-one | Drug Info | [528829] | |||
1-phenyl-4-(1-phenyl-1H-tetrazol-5-yl)butan-2-one | Drug Info | [530901] | |||
11-beta-HSD1 inhibitors | Drug Info | [543704] | |||
11-keto-beta-boswellicacid | Drug Info | [530656] | |||
11-keto-ursolic acid | Drug Info | [530656] | |||
11beta-hydroxysteroid dehydrogenase-1 (HSD1) inhibitors | Drug Info | [543704] | |||
2'-Monophosphoadenosine 5'-Diphosphoribose | Drug Info | [551393] | |||
2-(2-chlorophenylamino)-5-methylthiazol-4(5H)-one | Drug Info | [529083] | |||
2-(4-tosylpiperazin-1-yl)nicotinonitrile | Drug Info | [529500] | |||
2-(adamantan-1-ylamino)-5,5-diethyl-oxazol-4-one | Drug Info | [528929] | |||
2-(benzylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | [528929] | |||
2-(cyclooctylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | [528929] | |||
2-(N-Morpholino)-Ethanesulfonic Acid | Drug Info | [551393] | |||
2-(o-toluidino)-5-ethylthiazol-4(5H)-one | Drug Info | [529430] | |||
2-(o-toluidino)-5-isopropylthiazol-4(5H)-one | Drug Info | [529083] | |||
2-(phenylsulfonyl)-1-(thiophen-3-yl)ethanone | Drug Info | [528829] | |||
2-(phenylsulfonyl)-1-p-tolylethanone | Drug Info | [528829] | |||
3-acetyl-11-keto-beta-boswellic acid | Drug Info | [530656] | |||
3-acetyl-11-keto-ursolic acid | Drug Info | [530656] | |||
3-benzyl-1-cyclohexylpyrrolidin-2-one | Drug Info | [528391] | |||
3-epicorosolic acid methyl ester | Drug Info | [530656] | |||
5,5-diethyl-2-(phenethylamino)oxazol-4(5H)-one | Drug Info | [528929] | |||
5-isopropyl-2-(phenylamino)thiazol-4(5H)-one | Drug Info | [529083] | |||
A-849531 | Drug Info | [543704] | |||
Abietic acid | Drug Info | [535877] | |||
Adamantan-1-yl-(4-ethyl-piperazin-1-yl)-methanone | Drug Info | [528722] | |||
Adamantan-1-yl-piperazin-1-yl-methanone | Drug Info | [528722] | |||
Adamantan-1-yl-piperidin-1-yl-methanone | Drug Info | [528722] | |||
Adamantan-1-yl-pyrrolidin-1-yl-methanone | Drug Info | [528722] | |||
Adamantan-2-yl-piperidin-1-yl-methanone | Drug Info | [528722] | |||
AMG-221 | Drug Info | [530911] | |||
AZD-4017 | Drug Info | [551800] | |||
AZD8329 | Drug Info | [550290] | |||
BMS-816336 | Drug Info | [548678] | |||
BVT-3498 | Drug Info | [531312] | |||
BVT.2733 | Drug Info | [535789] | |||
Carbenoxolone | Drug Info | [535911], [536921], [537302] | |||
CNX-010 | Drug Info | [543704] | |||
Corosolic acid | Drug Info | [530656] | |||
Enoxolone | Drug Info | [535911] | |||
EQ-1280 | Drug Info | [543704] | |||
FIG 1 | Drug Info | [529441] | |||
Flavanone | Drug Info | [535877] | |||
GLYCYRRHIZIN | Drug Info | [530246] | |||
HPP-851 | Drug Info | [548698] | |||
INCB13739 | Drug Info | [551127] | |||
JTT-654 | Drug Info | [551800] | |||
LY-2523199 | Drug Info | [549810] | |||
MERCK-544 | Drug Info | [530715] | |||
N-benzyl-N-(phenylsulfonyl)benzamide | Drug Info | [528829] | |||
PF-877423 | Drug Info | [530826] | |||
PF-915275 | Drug Info | [530170] | |||
Piperidine-1-carboxylic acid adamantan-2-yl ester | Drug Info | [531176] | |||
Piperidine-1-carboxylic acid adamantan-2-ylamide | Drug Info | [531176] | |||
RG-4929 | Drug Info | [551800] | |||
SKI-2852 | Drug Info | [543704] | |||
Tormentic acid methyl ester | Drug Info | [530656] | |||
URSOLIC ACID | Drug Info | [530656] | |||
Modulator | BI-135585 | Drug Info | [551800] | ||
BMS-770767 | Drug Info | [551800] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Steroid hormone biosynthesis | ||||
Metabolism of xenobiotics by cytochrome P450 | |||||
Metabolic pathways | |||||
Chemical carcinogenesis | |||||
NetPath Pathway | IL1 Signaling Pathway | ||||
FSH Signaling Pathway | |||||
PathWhiz Pathway | Steroidogenesis | ||||
Reactome | Glucocorticoid biosynthesis | ||||
WikiPathways | Prostaglandin Synthesis and Regulation | ||||
Metabolism of steroid hormones and vitamin D | |||||
Glucocorticoid & | |||||
Mineralcorticoid Metabolism | |||||
References | |||||
Ref 467927 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4688). | ||||
Ref 522347 | ClinicalTrials.gov (NCT00698230) Safety and Efficacy of INCB013739 Plus Metformin Compared to Metformin Alone on Glycemic Control in Type 2 Diabetics. U.S. National Institutes of Health. | ||||
Ref 522787 | ClinicalTrials.gov (NCT00979368) Safety Study of BMS-816336 in Healthy Male Subjects. U.S. National Institutes of Health. | ||||
Ref 522793 | ClinicalTrials.gov (NCT00983086) Effects of Consumption of Orange Juice on Vascular Protection and Immune Function: Clinical Study on the Specific Contribution of Citrus Flavanones. U.S. National Institutes of Health. | ||||
Ref 522824 | ClinicalTrials.gov (NCT00997152) Efficacy and Safety Study of JTT-654 in Type 2 Diabetic Patients. U.S. National Institutes of Health. | ||||
Ref 522932 | ClinicalTrials.gov (NCT01058083) Safety Study of BMS-770767 in Subjects With Hypercholesterolemia. U.S. National Institutes of Health. | ||||
Ref 523126 | ClinicalTrials.gov (NCT01173471) A Phase IIa Study to Assess the Tolerability, Safety, and Efficacy of AZD4017 for Raised Intra-ocular Pressure. U.S. National Institutes of Health. | ||||
Ref 523331 | ClinicalTrials.gov (NCT01282970) Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 135585 XX in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
Ref 523449 | ClinicalTrials.gov (NCT01342185) Efficacy of Medical Ozone Therapy in Patients With Chronic Hepatitis B. U.S. National Institutes of Health. | ||||
Ref 523728 | ClinicalTrials.gov (NCT01493271) A Study of RO5093151 in Patients With Ocular Hypertension Or Open Angle Glaucoma. U.S. National Institutes of Health. | ||||
Ref 540674 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 408). | ||||
Ref 542670 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7695). | ||||
Ref 542690 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7715). | ||||
Ref 547606 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017768) | ||||
Ref 548447 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025590) | ||||
Ref 548697 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027759) | ||||
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 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 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 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 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 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 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 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 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 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 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 530715 | Bioorg Med Chem Lett. 2010 Mar 1;20(5):1551-4. Epub 2010 Jan 25.Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors. | ||||
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 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 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 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 535789 | Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology. 2003 Nov;144(11):4755-62. Epub 2003 Jul 31. | ||||
Ref 535877 | A rapid screening assay for inhibitors of 11beta-hydroxysteroid dehydrogenases (11beta-HSD): flavanone selectively inhibits 11beta-HSD1 reductase activity. Mol Cell Endocrinol. 2003 Dec 30;212(1-2):41-9. | ||||
Ref 535911 | Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J Biol Chem. 2004 Apr 30;279(18):18415-24. Epub 2004 Feb 18. | ||||
Ref 536921 | Mediators of mineralocorticoid receptor-induced profibrotic inflammatory responses in the heart. Clin Sci (Lond). 2009 May;116(9):731-9. | ||||
Ref 537302 | Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):248-52. Epub 2009 Feb 7. | ||||
Ref 543704 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2763). | ||||
Ref 548678 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027626) | ||||
Ref 548698 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027759) | ||||
Ref 549810 | Repurposing Diabetes Drugs for Brain Insulin Resistance in Alzheimer Disease. before print June 15, 2014. |
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