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The next generation of DNMT inhibitors

DNA methyltransferase inhibitors are widely used in preclinical and clinical studies, but poor pharmacokinetics and low efficacy in solid tumors limit their therapeutic use. A new study reports the development and characterization of a specific, non-covalent DNA methyltransferase inhibitor with more-durable DNA hypomethylation and lower toxicity than that of nucleoside analogs.

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Fig. 1: Mechanism of DNMT1 inhibition by GSK3685032 versus that of AZA and DAC.

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Correspondence to Daniel D. De Carvalho.

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D.D.D.C. received research funds from Pfizer and Nektar Therapeutics, and is co-founder and chief scientific officer at Adela.

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Mehdipour, P., Chen, R. & De Carvalho, D.D. The next generation of DNMT inhibitors. Nat Cancer 2, 1000–1001 (2021). https://doi.org/10.1038/s43018-021-00271-z

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