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DNA methyltransferase 1

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Target id: 2605

Nomenclature: DNA methyltransferase 1

Family: 2.1.1.- Methyltransferases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1616 19p13.2 DNMT1 DNA methyltransferase 1
Mouse - 1620 9 7.66 cM Dnmt1 DNA methyltransferase 1
Rat - 1622 8q13 Dnmt1 DNA methyltransferase 1
Previous and Unofficial Names Click here for help
CXXC9 | MCMT | DNA (cytosine-5-)-methyltransferase 1 | DNA methyltransferase (cytosine-5) 1
Database Links Click here for help
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction Click here for help
EC Number:

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
bromo-deaza-SAH Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pKi 5
pKi 6.0 (Ki 9.5x10-7 M) [5]
GSK3685032 Small molecule or natural product Hs Inhibition 6.6 pIC50 2
pIC50 6.6 (IC50 2.3x10-7 M) [2]
Description: Determined using a fluorescence-coupled breaklight assay and full-length hDNMT1
CM-272 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 3
pIC50 6.4 (IC50 3.62x10-7 M) [3]
SGI-1027 Small molecule or natural product Hs Inhibition 6.1 pIC50 4
pIC50 6.1 (IC50 8.5x10-7 M) [4]
Description: Value derived from a nanoscale HTS assay.
Inhibitor Comments
Azacitidine and decitabine are likely to be inhibitors of DNMT1 and DNMT3A. We infer primary target designation from reports of drug action in in vitro and in vivo studies despite the paucity of pharmacological affinity data.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant; ADCADN
OMIM: 604121
Orphanet: ORPHA314404
Disease:  Neuropathy, hereditary sensory, type IE; HSN1E
Disease Ontology: DOID:0050548
OMIM: 614116
General Comments
Based on in vitro analysis, DNMT1 is proposed to bind the ORF8 protein of the SARS-CoV-2 virus [1], although the relevance of this interaction is unclear.


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1. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583 (7816): 459-468. [PMID:32353859]

2. Pappalardi MB, Keenan K, Cockerill M, Kellner WA, Stowell A, Sherk C, Wong K, Pathuri S, Briand J,Steidel M et al.. (2021) Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nature Cancer, [Epub ahead of print]. DOI: 10.1038/s43018-021-00249-x

3. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A et al.. (2017) Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies. Nat Commun, 8: 15424. [PMID:28548080]

4. Valente S, Liu Y, Schnekenburger M, Zwergel C, Cosconati S, Gros C, Tardugno M, Labella D, Florean C, Minden S et al.. (2014) Selective non-nucleoside inhibitors of human DNA methyltransferases active in cancer including in cancer stem cells. J Med Chem, 57 (3): 701-13. [PMID:24387159]

5. Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH et al.. (2013) Bromo-deaza-SAH: a potent and selective DOT1L inhibitor. Bioorg Med Chem, 21 (7): 1787-94. [PMID:23433670]

How to cite this page

2.1.1.- Methyltransferases: DNA methyltransferase 1. Last modified on 26/03/2024. Accessed on 13/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY,