Target Information
Target General Information | Top | |||||
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Target ID |
T65200
(Former ID: TTDC00070)
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Target Name |
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)
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Synonyms |
HSD11B1; 11beta-HSD1A; 11HSD1; 11-beta-hydroxysteroid dehydrogenase 1; 11-beta-HSD1; 11-DH; 11 beta-hydroxysteroid dehydrogenase type 1
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Gene Name |
HSD11B1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Influenza [ICD-11: 1E30-1E32] | |||||
2 | Lupus erythematosus [ICD-11: 4A40] | |||||
3 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
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.
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BioChemical Class |
Short-chain dehydrogenases reductase
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UniProt ID | ||||||
EC Number |
EC 1.1.1.146
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Sequence |
MAFMKKYLLPILGLFMAYYYYSANEEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAH
VVVTARSKETLQKVVSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNH ITNTSLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKVAYPMV AAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMKAVSGIVHMQAAPKEE CALEIIKGGALRQEEVYYDSSLWTTLLIRNPCRKILEFLYSTSYNMDRFINK Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T40DIM |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 12 Clinical Trial Drugs | + | ||||
1 | BVT.2733 | Drug Info | Phase 3 | Lupus | [2] | |
2 | GLYCYRRHIZIN | Drug Info | Phase 3 | Influenza virus infection | [3], [4] | |
3 | INCB13739 | Drug Info | Phase 2a | Type-2 diabetes | [5] | |
4 | AZD-4017 | Drug Info | Phase 2 | Ocular hypertension | [6], [7] | |
5 | BMS-770767 | Drug Info | Phase 2 | Hypercholesterolaemia | [8] | |
6 | JTT-654 | Drug Info | Phase 2 | Type-2 diabetes | [9] | |
7 | RG-4929 | Drug Info | Phase 2 | Metabolic disorder | [10] | |
8 | UE-2343 | Drug Info | Phase 2 | Alzheimer disease | [11], [12] | |
9 | URSOLIC ACID | Drug Info | Phase 2 | Metabolic syndrome x | [13] | |
10 | AZD8329 | Drug Info | Phase 1 | Obesity | [14], [15] | |
11 | BI-135585 | Drug Info | Phase 1 | Type-2 diabetes | [16] | |
12 | BMS-816336 | Drug Info | Phase 1 | Lipid metabolism disorder | [17] | |
Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
1 | LY-2523199 | Drug Info | Discontinued in Phase 2 | Type-2 diabetes | [18] | |
2 | AMG-221 | Drug Info | Discontinued in Phase 1 | Metabolic disorder | [19] | |
3 | PF-915275 | Drug Info | Discontinued in Phase 1 | Non-insulin dependent diabetes | [20] | |
4 | BVT-3498 | Drug Info | Terminated | Metabolic disorder | [22] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | HPP-851 | Drug Info | Preclinical | Metabolic disorder | [21] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 81 Inhibitor drugs | + | ||||
1 | BVT.2733 | Drug Info | [1] | |||
2 | GLYCYRRHIZIN | Drug Info | [23] | |||
3 | INCB13739 | Drug Info | [24] | |||
4 | AZD-4017 | Drug Info | [25] | |||
5 | JTT-654 | Drug Info | [25] | |||
6 | RG-4929 | Drug Info | [25] | |||
7 | UE-2343 | Drug Info | [11], [12] | |||
8 | URSOLIC ACID | Drug Info | [26] | |||
9 | AZD8329 | Drug Info | [15] | |||
10 | BMS-816336 | Drug Info | [27] | |||
11 | LY-2523199 | Drug Info | [28] | |||
12 | AMG-221 | Drug Info | [29] | |||
13 | PF-915275 | Drug Info | [30] | |||
14 | HPP-851 | Drug Info | [31] | |||
15 | BVT-3498 | Drug Info | [22] | |||
16 | (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE | Drug Info | [32] | |||
17 | (4-methoxyphenyl)(4-phenylazepan-1-yl)methanone | Drug Info | [33] | |||
18 | 1,1-diphenyl-3-(phenylsulfonyl)propan-2-one | Drug Info | [34] | |||
19 | 1-(1-phenyl-1H-tetrazol-5-ylthio)propan-2-one | Drug Info | [35] | |||
20 | 1-(2-adamantyl)-3-benzylpyrrolidin-2-one | Drug Info | [36] | |||
21 | 1-(3,4-dichlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
22 | 1-(3,5-dimethylphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
23 | 1-(3-chloropyridin-2-yl)-4-tosylpiperazine | Drug Info | [37] | |||
24 | 1-(3-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
25 | 1-(3-methylpyridin-2-yl)-4-tosylpiperazine | Drug Info | [37] | |||
26 | 1-(3-nitropyridin-2-yl)-4-tosylpiperazine | Drug Info | [37] | |||
27 | 1-(4-chlorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
28 | 1-(4-chlorophenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [33] | |||
29 | 1-(4-ethylphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [33] | |||
30 | 1-(4-ethylpiperazin-1-yl)-2-phenylethanone | Drug Info | [38] | |||
31 | 1-(4-fluorophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
32 | 1-(4-fluorophenyl)-3-(phenylsulfonyl)propan-1-one | Drug Info | [34] | |||
33 | 1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
34 | 1-(4-methoxyphenylsulfonyl)-4-phenylazepan-4-ol | Drug Info | [33] | |||
35 | 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone | Drug Info | [34] | |||
36 | 1-(4-tert-butylphenylsulfonyl)-4-methoxyazepane | Drug Info | [33] | |||
37 | 1-(4-tert-butylphenylsulfonyl)azepan-4-ol | Drug Info | [33] | |||
38 | 1-(phenylsulfonyl)butan-2-one | Drug Info | [34] | |||
39 | 1-phenyl-2-(1-phenyl-1H-tetrazol-5-yloxy)ethanone | Drug Info | [35] | |||
40 | 1-phenyl-3-(phenylsulfonyl)propan-1-one | Drug Info | [34] | |||
41 | 1-phenyl-4-(1-phenyl-1H-tetrazol-5-yl)butan-2-one | Drug Info | [35] | |||
42 | 11-keto-beta-boswellicacid | Drug Info | [26] | |||
43 | 11-keto-ursolic acid | Drug Info | [26] | |||
44 | 2'-Monophosphoadenosine 5'-Diphosphoribose | Drug Info | [39] | |||
45 | 2-(2-chlorophenylamino)-5-methylthiazol-4(5H)-one | Drug Info | [40] | |||
46 | 2-(4-tosylpiperazin-1-yl)nicotinonitrile | Drug Info | [37] | |||
47 | 2-(adamantan-1-ylamino)-5,5-diethyl-oxazol-4-one | Drug Info | [41] | |||
48 | 2-(benzylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | [41] | |||
49 | 2-(cyclooctylamino)-5,5-diethyloxazol-4(5H)-one | Drug Info | [41] | |||
50 | 2-(N-Morpholino)-Ethanesulfonic Acid | Drug Info | [39] | |||
51 | 2-(o-toluidino)-5-ethylthiazol-4(5H)-one | Drug Info | [42] | |||
52 | 2-(o-toluidino)-5-isopropylthiazol-4(5H)-one | Drug Info | [40] | |||
53 | 2-(phenylsulfonyl)-1-(thiophen-3-yl)ethanone | Drug Info | [34] | |||
54 | 2-(phenylsulfonyl)-1-p-tolylethanone | Drug Info | [34] | |||
55 | 3-acetyl-11-keto-beta-boswellic acid | Drug Info | [26] | |||
56 | 3-acetyl-11-keto-ursolic acid | Drug Info | [26] | |||
57 | 3-benzyl-1-cyclohexylpyrrolidin-2-one | Drug Info | [36] | |||
58 | 3-epicorosolic acid methyl ester | Drug Info | [26] | |||
59 | 5,5-diethyl-2-(phenethylamino)oxazol-4(5H)-one | Drug Info | [41] | |||
60 | 5-isopropyl-2-(phenylamino)thiazol-4(5H)-one | Drug Info | [40] | |||
61 | A-849531 | Drug Info | [43] | |||
62 | Abietic acid | Drug Info | [44] | |||
63 | Adamantan-1-yl-(4-ethyl-piperazin-1-yl)-methanone | Drug Info | [38] | |||
64 | Adamantan-1-yl-piperazin-1-yl-methanone | Drug Info | [38] | |||
65 | Adamantan-1-yl-piperidin-1-yl-methanone | Drug Info | [38] | |||
66 | Adamantan-1-yl-pyrrolidin-1-yl-methanone | Drug Info | [38] | |||
67 | Adamantan-2-yl-piperidin-1-yl-methanone | Drug Info | [38] | |||
68 | Carbenoxolone | Drug Info | [45], [46], [47] | |||
69 | CNX-010 | Drug Info | [43] | |||
70 | Corosolic acid | Drug Info | [26] | |||
71 | EQ-1280 | Drug Info | [43] | |||
72 | FIG 1 | Drug Info | [48] | |||
73 | Flavanone | Drug Info | [44] | |||
74 | MERCK-544 | Drug Info | [49] | |||
75 | N-benzyl-N-(phenylsulfonyl)benzamide | Drug Info | [34] | |||
76 | PF-877423 | Drug Info | [50] | |||
77 | Piperidine-1-carboxylic acid adamantan-2-yl ester | Drug Info | [51] | |||
78 | Piperidine-1-carboxylic acid adamantan-2-ylamide | Drug Info | [51] | |||
79 | SKI-2852 | Drug Info | [43] | |||
80 | Tormentic acid methyl ester | Drug Info | [26] | |||
81 | [(125)I] RB129 | Drug Info | [47] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | BMS-770767 | Drug Info | [25] | |||
2 | BI-135585 | Drug Info | [25] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
1 | Steroid hormone biosynthesis | |||||
2 | Metabolism of xenobiotics by cytochrome P450 | |||||
3 | Metabolic pathways | |||||
4 | Chemical carcinogenesis | |||||
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | IL1 Signaling Pathway | |||||
2 | FSH Signaling Pathway | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Steroidogenesis | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Glucocorticoid biosynthesis | |||||
WikiPathways | [+] 3 WikiPathways | + | ||||
1 | Prostaglandin Synthesis and Regulation | |||||
2 | Metabolism of steroid hormones and vitamin D | |||||
3 | Glucocorticoid & Mineralcorticoid Metabolism |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology. 2003 Nov;144(11):4755-62. | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | URL: 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 4 | ClinicalTrials.gov (NCT01342185) Efficacy of Medical Ozone Therapy in Patients With Chronic Hepatitis B. U.S. National Institutes of Health. | |||||
REF 5 | 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 6 | URL: 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 7 | 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 8 | ClinicalTrials.gov (NCT01058083) Safety Study of BMS-770767 in Subjects With Hypercholesterolemia. U.S. National Institutes of Health. | |||||
REF 9 | ClinicalTrials.gov (NCT00997152) Efficacy and Safety Study of JTT-654 in Type 2 Diabetic Patients. U.S. National Institutes of Health. | |||||
REF 10 | ClinicalTrials.gov (NCT01493271) A Study of RO5093151 in Patients With Ocular Hypertension Or Open Angle Glaucoma. U.S. National Institutes of Health. | |||||
REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 12 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 13 | ClinicalTrials.gov (NCT02337933) Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome. U.S. National Institutes of Health. | |||||
REF 14 | URL: 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 15 | Clinical pipeline report, company report or official report of AstraZeneca (2011). | |||||
REF 16 | 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 17 | ClinicalTrials.gov (NCT00979368) Safety Study of BMS-816336 in Healthy Male Subjects. U.S. National Institutes of Health. | |||||
REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034519) | |||||
REF 19 | 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 20 | 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 21 | 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 22 | Current and future drug targets in weight management. Pharm Res. 2011 Aug;28(8):1792-818. | |||||
REF 23 | Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. Bioorg Med Chem. 2009 Aug 1;17(15):5722-32. | |||||
REF 24 | Incyte's Selective Oral Inhibitor Of 11beta-HSD1 Demonstrates Improvements In Insulin Sensitivity And Lowers Cholesterol Levels In Type 2 Diabetics. Incyte. 2008. | |||||
REF 25 | New Therapeutic Strategies for Type 2 Diabetes: Small Molecule Approaches. 2012. Chapter 5. Page(131). | |||||
REF 26 | 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational a... Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. | |||||
REF 27 | 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 28 | Repurposing Diabetes Drugs for Brain Insulin Resistance in Alzheimer Disease. before print June 15, 2014. | |||||
REF 29 | Discovery of a potent, orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-b... J Med Chem. 2010 Jun 10;53(11):4481-7. | |||||
REF 30 | N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. | |||||
REF 31 | 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 32 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 33 | The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. | |||||
REF 34 | beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action. Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. | |||||
REF 35 | Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. | |||||
REF 36 | Discovery of orally active butyrolactam 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5555-60. | |||||
REF 37 | Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. | |||||
REF 38 | Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2838-43. | |||||
REF 39 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 40 | The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. | |||||
REF 41 | Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4837-40. | |||||
REF 42 | 2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure an... J Med Chem. 2008 May 22;51(10):2933-43. | |||||
REF 43 | URL: 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 44 | 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 45 | 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. | |||||
REF 46 | Mediators of mineralocorticoid receptor-induced profibrotic inflammatory responses in the heart. Clin Sci (Lond). 2009 May;116(9):731-9. | |||||
REF 47 | Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, a... J Biol Chem. 2004 Apr 30;279(18):18415-24. | |||||
REF 48 | 4-Methyl-5-phenyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3405-11. | |||||
REF 49 | Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1551-4. | |||||
REF 50 | The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2010 May 1;20(9):2897-902. | |||||
REF 51 | Discovery and optimization of adamantyl carbamate inhibitors of 11-HSD1. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6725-9. |
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