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enhancer of zeste 1 polycomb repressive complex 2 subunit

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Target id: 2835

Nomenclature: enhancer of zeste 1 polycomb repressive complex 2 subunit

Abbreviated Name: EZH1

Family: 2.1.1.43 Histone methyltransferases (HMTs)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 747 17q21.2 EZH1 enhancer of zeste 1 polycomb repressive complex 2 subunit 1
Mouse - 747 11 64.37 cM Ezh1 enhancer of zeste 1 polycomb repressive complex 2 subunit
Rat - 747 10q32.1 Ezh1 enhancer of zeste 1 polycomb repressive complex 2 subunit
Previous and Unofficial Names Click here for help
enhancer of zeste homolog 1 (Drosophila) | KMT6B
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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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
tulmimetostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 10.2 pIC50 3
pIC50 10.2 (IC50 6x10-11 M) [3]
Description: Inhibition of catalytic activity of wild-type EZH1-containing PRC2 complex in a biochemical assay
valemetostat Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.8 pIC50 4
pIC50 7.8 (IC50 1.6x10-8 M) [4]
GSK343 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 5
pIC50 6.6 (IC50 2.4x10-7 M) [5]
General Comments
EZH1/2 inhibitors have anti-proliferative effects that have anti-cancer potential. In addition, pharmacological inhibition of EZH1 and EZH2 has been shown to induce multiple inflammatory, stress, and antipathogen pathways, and to enhance recruitment of immune cells to virally infected cells in vitro, thereby creating a cellular antiviral state that was suppressive to infection by a range of DNA and RNA viruses [2]. EZH1/2 inhibitors exhibiting this experimental effect were GSK126, GSK343 and UNC1999. This work suggests that EZH1/2 inhibitors can induce a general antiviral defense mechanism.

References

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1. Abel KJ, Brody LC, Valdes JM, Erdos MR, McKinley DR, Castilla LH, Merajver SD, Couch FJ, Friedman LS, Ostermeyer EA et al.. (1996) Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1. Genomics, 37 (2): 161-71. [PMID:8921387]

2. Arbuckle JH, Gardina PJ, Gordon DN, Hickman HD, Yewdell JW, Pierson TC, Myers TG, Kristie TM. (2017) Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens. MBio, 8 (4). [PMID:28811345]

3. Bradley WD. (2022) Ezh2 inhibition in combination therapies for the treatment of cancers. Patent number: US20220257577A1. Assignee: Constellation Pharmaceuticals Inc. Priority date: 23/07/2020. Publication date: 18/08/2022.

4. Honma D, Kanno O, Watanabe J, Kinoshita J, Hirasawa M, Nosaka E, Shiroishi M, Takizawa T, Yasumatsu I, Horiuchi T et al.. (2017) Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor. Cancer Sci, 108 (10): 2069-2078. [PMID:28741798]

5. Verma SK, Tian X, LaFrance LV, Duquenne C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA et al.. (2012) Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett, 3 (12): 1091-6. [PMID:24900432]

How to cite this page

2.1.1.43 Histone methyltransferases (HMTs): enhancer of zeste 1 polycomb repressive complex 2 subunit. Last modified on 19/04/2023. Accessed on 13/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2835.