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hydroxysteroid 11-beta dehydrogenase 1

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Target not currently curated in GtoImmuPdb

Target id: 2763

Nomenclature: hydroxysteroid 11-beta dehydrogenase 1

Abbreviated Name: 11-βHSD1

Family: 1.-.-.- Oxidoreductases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 292 1q32.2 HSD11B1 hydroxysteroid 11-beta dehydrogenase 1
Mouse 1 292 1 H6 Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1
Rat 1 288 13q27 Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1
Previous and Unofficial Names Click here for help
11β-HSD | 11b-HSD | corticosteroid 11-beta-dehydrogenase isozyme 1 | HSD11B | hydroxysteroid (11-beta) dehydrogenase 1
Database Links Click here for help
Alphafold P28845 (Hs), P50172 (Mm), P16232 (Rn)
BRENDA 1.1.1.146
ChEMBL Target CHEMBL4235 (Hs), CHEMBL3910 (Mm), CHEMBL2391 (Rn)
Ensembl Gene ENSG00000117594 (Hs), ENSMUSG00000016194 (Mm), ENSRNOG00000005861 (Rn)
Entrez Gene 3290 (Hs), 15483 (Mm), 25116 (Rn)
Human Protein Atlas ENSG00000117594 (Hs)
KEGG Enzyme 1.1.1.146
KEGG Gene hsa:3290 (Hs), mmu:15483 (Mm), rno:25116 (Rn)
Pharos P28845 (Hs)
RefSeq Nucleotide NM_005525 (Hs), NM_181755 (Hs), NM_001206741 (Hs), NM_008288 (Mm), NM_001044751 (Mm), NM_017080 (Rn)
RefSeq Protein NP_005516 (Hs), NP_861420 (Hs), NP_001193670 (Hs), NP_001038216 (Mm), NP_032314 (Mm), NP_058776 (Rn)
SynPHARM 85793 (in complex with BMS-823778)
UniProtKB P28845 (Hs), P50172 (Mm), P16232 (Rn)
Wikipedia HSD11B1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human 11-beta-hydroxysteroid-dehydrogenase Bound to an Ortho-chlro-sulfonyl-piperazine Inhibitor
PDB Id:  3H6K
Ligand:  KB-74935
Resolution:  2.19Å
Species:  Human
References:  7
Enzyme Reaction Click here for help
EC Number: 1.1.1.146

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ABT-384 Small molecule or natural product Primary target of this compound Hs Inhibition 8.1 pKi 6
⤷ pKi 8.1 (Ki 9x10-9 M) [6]
AZD4017 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.7 pIC50 5
⤷ pIC50 8.7 (IC50 2x10-9 M) [5]
BMS-823778 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.6 pIC50 4
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [4]
INCB13739 Small molecule or natural product Hs Inhibition 8.5 pIC50 10
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [10]
AZD8329 Small molecule or natural product Primary target of this compound Hs Inhibition 8.1 pIC50 1
⤷ pIC50 8.1 (IC50 9x10-9 M) [1]
enoxolone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 – 7.9 pIC50 3,9
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [9]
pIC50 7.5 (IC50 2.9x10-8 M) [3]
UE2343 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 8
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [8]
enoxolone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 9x10-8 M) [2]
View species-specific inhibitor tables
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cortisone reductase deficiency 2
Synonyms: Hyperandrogenism due to cortisone reductase deficiency [Orphanet: ORPHA168588]
OMIM: 614662
Orphanet: ORPHA168588
General Comments
HSD11B1 reduces cortisone to the active hormone cortisol.

References

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1. AstraZeneca. AZD8329. Accessed on 12/09/2014. Modified on 12/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd8329/

2. Beseda I, Czollner L, Shah PS, Khunt R, Gaware R, Kosma P, Stanetty C, Del Ruiz-Ruiz MC, Amer H, Mereiter K et al.. (2010) Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases. Bioorg Med Chem, 18 (1): 433-54. [PMID:19914836]

3. Chen XQ, Shao LD, Pal M, Shen Y, Cheng X, Xu G, Peng LY, Wang K, Pan ZH, Li MM et al.. (2015) Hupehenols A-E, selective 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors from Viburnum hupehense. J Nat Prod, 78 (2): 330-4. [PMID:25590374]

4. Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, O'Connor SP, Ye XY, Chen S, Wu S et al.. (2018) Discovery of Clinical Candidate BMS-823778 as an Inhibitor of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1). ACS Med Chem Lett, 9 (12): 1170-1174. DOI: 10.1021/acsmedchemlett.8b00307 [PMID:30613321]

5. Scott JS, Bowker SS, Deschoolmeester J, Gerhardt S, Hargreaves D, Kilgour E, Lloyd A, Mayers RM, McCoull W, Newcombe NJ et al.. (2012) Discovery of a potent, selective, and orally bioavailable acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017). J Med Chem, 55 (12): 5951-64. [PMID:22691057]

6. Sorensen B, Rohde J, Wang J, Fung S, Monzon K, Chiou W, Pan L, Deng X, Stolarik D, Frevert EU et al.. (2006) Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction. Bioorg Med Chem Lett, 16 (23): 5958-62. [PMID:16996734]

7. Wan ZK, Chenail E, Xiang J, Li HQ, Ipek M, Bard J, Svenson K, Mansour TS, Xu X, Tian X et al.. (2009) Efficacious 11beta-hydroxysteroid dehydrogenase type I inhibitors in the diet-induced obesity mouse model. J Med Chem, 52 (17): 5449-61. [PMID:19673466]

8. Webster SP, McBride A, Binnie M, Sooy K, Seckl JR, Andrew R, Pallin TD, Hunt HJ, Perrior TR, Ruffles VS et al.. (2017) Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™). Br J Pharmacol, 174 (5): 396-408. [PMID:28012176]

9. Yang H, Shen Y, Chen J, Jiang Q, Leng Y, Shen J. (2009) Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors. Eur J Med Chem, 44 (3): 1167-71. [PMID:18653260]

10. Zhang C, Xu M, He C, Zhuo J, Burns DM, Qian DQ, Lin Q, Li YL, Chen L, Shi E et al.. (2022) Discovery of 1'-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3'-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach. Bioorg Med Chem Lett, 69: 128782. [PMID:35537608]

How to cite this page

1.-.-.- Oxidoreductases: hydroxysteroid 11-beta dehydrogenase 1. Last modified on 09/08/2022. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2763.