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Updated: May 30, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Trimethylaurintricarboxylic acid inhibits human DNA methyltransferase 1: insights from enzymatic and molecular
Jakyung Yoo1, José L Medina-Franco
1Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
Abstract:
DNA methyltransferase 1 (DNMT1) is an emerging target for the treatment of cancer, brain disorders, and other diseases. Currently, there are only a few DNMT1 inhibitors with potential application as therapeutic agents or research tools. 5,5-Methylenedisalicylic acid is a novel scaffold previously identified by virtual screening with detectable although weak inhibitory activity of DNMT1 in biochemical assays. Herein, we report enzyme inhibition of a structurally related compound, trimethylaurintricarboxylic acid (NSC97317) that showed a low micromolar inhibition of DNMT1 (IC(50) = 4.79 μM). Docking studies of the new inhibitor with the catalytic domain of DNMT1 suggest that NSC97317 can bind into the catalytic site. Interactions with amino acid residues that participate in the mechanism of DNA methylation contribute to the binding recognition. In addition, NSC97317 had a good match with a structure-based pharmacophore model recently developed for inhibitors of DNMT1. Trimethylaurintricarboxylic acid can be a valuable biochemical tool to study DNMT1 inhibition in cancer and other diseases related to DNA methylation.
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