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First-in-Class Allosteric Inhibitors of DNMT3A Disrupt Protein-Protein Interactions and Induce Acute Myeloid Leukemia Cell Differentiation.

Journal of medicinal chemistry - 11 Aug 2022

Sandoval Jonathan E, Ramabadran Raghav, Stillson Nathaniel, Sarah Letitia, Fujimori Danica Galonić, Goodell Margaret A, Reich Norbert

Abstract excerpt

We previously identified two structurally related pyrazolone (compound 1) and pyridazine (compound 2) allosteric inhibitors of DNMT3A through screening of a small chemical library. Here, we show that these compounds bind and disrupt protein-protein interactions (PPIs) at the DNMT3A tetramer interface. This disruption is observed with distinct partner proteins and occurs even when the complexes are acting on DNA,...

Topics

Cell Differentiation
DNA (Cytosine-5-)-Methyltransferases
DNA Methyltransferase 3A
DNA Modification Methylases
Humans
Leukemia, Myeloid, Acute
Mutation

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Identifiers

PMID: 35866897
DOI: 10.1021/acs.jmedchem.2c00725

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 31 Aug 2026.

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