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egl-9 family hypoxia inducible factor 1

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Target id: 2833

Nomenclature: egl-9 family hypoxia inducible factor 1

Abbreviated Name: PHD2

Family: Prolyl hydroxylases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 426 1q42.2 EGLN1 egl-9 family hypoxia inducible factor 1
Mouse - 400 8 E2 Egln1 egl-9 family hypoxia-inducible factor 1
Rat - 338 19q12 Egln1 egl-9 family hypoxia-inducible factor 1
Previous and Unofficial Names Click here for help
EGL nine (C.elegans) homolog 1 | HIF prolyl hydroxylase 2 | HIFPH2 | SM-20 | ZMYND6 | egl-9 family hypoxia-inducible factor 1
Database Links Click here for help
Alphafold Q9GZT9 (Hs), Q91YE3 (Mm), P59722 (Rn)
BRENDA 1.14.11.29
ChEMBL Target CHEMBL5697 (Hs), CHEMBL3638322 (Rn)
Ensembl Gene ENSG00000135766 (Hs), ENSMUSG00000031987 (Mm), ENSRNOG00000063609 (Rn)
Entrez Gene 54583 (Hs), 112405 (Mm), 308913 (Rn)
Human Protein Atlas ENSG00000135766 (Hs)
KEGG Enzyme 1.14.11.29
KEGG Gene hsa:54583 (Hs), mmu:112405 (Mm), rno:308913 (Rn)
OMIM 606425 (Hs)
Pharos Q9GZT9 (Hs)
RefSeq Nucleotide NM_022051 (Hs), NM_053207 (Mm)
RefSeq Protein NP_071334 (Hs), NP_444437 (Mm)
UniProtKB Q9GZT9 (Hs), Q91YE3 (Mm), P59722 (Rn)
Wikipedia EGLN1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with vadadustat
PDB Id:  5OX6
Ligand:  vadadustat
Resolution:  1.99Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 1.14.11.29

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 6ee [PMID: 22364528] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.7 pIC50 5
⤷ pIC50 9.7 (IC50 2x10-10 M) [5]
IOX2 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 1
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [1]
vadadustat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 2,6
⤷ pIC50 7.5 (IC50 2.9x10-8 M) [2,6]
DDO-3055 Small molecule or natural product Hs Inhibition 7.2 pIC50 7
⤷ pIC50 7.2 (IC50 6.42x10-8 M) [7]
enarodustat Small molecule or natural product Approved drug Hs Inhibition 6.7 pIC50 3
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [3]
Description: Inhibition of PHD2 enzyme activity in a biochemical assay
IOX1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.5 pIC50 4
⤷ pIC50 4.5 (IC50 3.3x10-5 M) [4]
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Erythrocytosis, familial, 3; ECYT3
Synonyms: Autosomal dominant secondary polycythemia [Orphanet: ORPHA247511]
OMIM: 609820
Orphanet: ORPHA247511

References

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1. Chowdhury R, Candela-Lena JI, Chan MC, Greenald DJ, Yeoh KK, Tian YM, McDonough MA, Tumber A, Rose NR, Conejo-Garcia A et al.. (2013) Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases. ACS Chem Biol, 8 (7): 1488-96. [PMID:23683440]

2. Langley GW, Abboud MI, Lohans CT, Schofield CJ. (2019) Inhibition of a viral prolyl hydroxylase. Bioorg Med Chem, 27 (12): 2405-2412. [PMID:30737136]

3. Ogoshi Y, Matsui T, Mitani I, Yokota M, Terashita M, Motoda D, Ueyama K, Hotta T, Ito T, Hase Y et al.. (2017) Discovery of JTZ-951: A HIF Prolyl Hydroxylase Inhibitor for the Treatment of Renal Anemia. ACS Med Chem Lett, 8 (12): 1320-1325. [PMID:29259755]

4. Schiller R, Scozzafava G, Tumber A, Wickens JR, Bush JT, Rai G, Lejeune C, Choi H, Yeh TL, Chan MC et al.. (2014) A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem, 9 (3): 566-71. [PMID:24504543]

5. Vachal P, Miao S, Pierce JM, Guiadeen D, Colandrea VJ, Wyvratt MJ, Salowe SP, Sonatore LM, Milligan JA, Hajdu R et al.. (2012) 1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia. J Med Chem, 55 (7): 2945-59. [PMID:22364528]

6. Yeh TL, Leissing TM, Abboud MI, Thinnes CC, Atasoylu O, Holt-Martyn JP, Zhang D, Tumber A, Lippl K, Lohans CT et al.. (2017) Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Chem Sci, 8 (11): 7651-7668. [PMID:29435217]

7. Zhang X, Lei Y, Hu T, Wu Y, Li Z, Jiang Z, Yang C, Zhang L, You Q. (2020) Discovery of Clinical Candidate (5-(3-(4-Chlorophenoxy)prop-1-yn-1-yl)-3-hydroxypicolinoyl)glycine, an Orally Bioavailable Prolyl Hydroxylase Inhibitor for the Treatment of Anemia. J Med Chem, 63 (17): 10045-10060. [PMID:32787144]

How to cite this page

Prolyl hydroxylases: egl-9 family hypoxia inducible factor 1. Last modified on 26/06/2023. Accessed on 24/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2833.