Journal of Molecular Modeling

, Volume 18, Issue 4, pp 1583–1589 | Cite as

Trimethylaurintricarboxylic acid inhibits human DNA methyltransferase 1: insights from enzymatic and molecular modeling studies

  • Jakyung Yoo
  • José L. Medina-FrancoEmail author
Original Paper


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 (IC50 = 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.


Trimethylaurintricarboxylic acid (NSC97317) is a novel and low micromolar inhibitor of DNMT1


Cancer DNMT Docking Enzyme inhibition Epigenetics Methyltransferase 



NSC97317 was kindly supplied by the Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute. This work was supported by the Menopause & Women’s Health Research Center and the State of Florida, Executive Office of the Governor’s Office of Tourism, Trade, and Economic Development. Authors are grateful to Kyle Kryak for proofreading the manuscript.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Torrey Pines Institute for Molecular StudiesPort St. LucieUSA

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