hydroxysteroid 11-beta dehydrogenase 1 | 1.-.-.- Oxidoreductases | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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hydroxysteroid 11-beta dehydrogenase 1

Target id: 2763

Nomenclature: hydroxysteroid 11-beta dehydrogenase 1

Abbreviated Name: 11-βHSD1

Family: 1.-.-.- Oxidoreductases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 292 1q32-q41 HSD11B1 hydroxysteroid 11-beta dehydrogenase 1
Mouse - 292 1 97.67 cM Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1
Rat - 288 13q27 Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1
Previous and Unofficial Names
11β-HSD | 11b-HSD | corticosteroid 11-beta-dehydrogenase isozyme 1 | HSD11B | hydroxysteroid (11-beta) dehydrogenase 1
Database Links
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)
RefSeq Nucleotide NM_181755 (Hs), NM_005525 (Hs), NM_001206741 (Hs), NM_001044751 (Mm), NM_008288 (Mm), NM_017080 (Rn)
RefSeq Protein NP_005516 (Hs), NP_001193670 (Hs), NP_861420 (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
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:  5
Enzyme Reaction
EC Number: 1.1.1.146

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ABT-384 Hs Inhibition 8.1 pKi 4
⤷ pKi 8.1 (Ki 9x10-9 M) [4]
AZD4017 Hs Inhibition 8.7 pIC50 3
⤷ pIC50 8.7 (IC50 2x10-9 M) [3]
BMS-823778 Hs Inhibition 8.6 pIC50 2
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [2]
AZD8329 Hs Inhibition 8.1 pIC50 1
⤷ pIC50 8.1 (IC50 9x10-9 M) [1]
Clinically-Relevant Mutations and Pathophysiology
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. Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, O'Connor SP, Ye X, 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 Medicinal Chemistry Lettere, Article ASAP. DOI: 10.1021/acsmedchemlett.8b00307

3. 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]

4. 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]

5. 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]

How to cite this page

1.-.-.- Oxidoreductases: hydroxysteroid 11-beta dehydrogenase 1. Last modified on 12/12/2018. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2763.