Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).

J Med Chem

Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.

Published: August 2023

Nuclear receptor binding SET domain proteins (NSDs) catalyze the mono- or dimethylation of histone 3 lysine 36 (H3K36me1 and H3K36me2), using -adenosyl-l-methionine (SAM) as a methyl donor. As a key member of the NSD family of proteins, NSD2 plays an important role in the pathogenesis and progression of various diseases such as cancers, inflammations, and infectious diseases, serving as a promising drug target. Developing potent and specific NSD2 inhibitors may provide potential novel therapeutics. Several NSD2 inhibitors and degraders have been discovered while remaining in the early stage of drug development. Excitingly, KTX-1001, a selective NSD2 inhibitor, has entered clinical trials. In this Perspective, the structures and functions of NSD2, its roles in various human diseases, and the recent advances in drug discovery strategies targeting NSD2 have been summarized. The challenges, opportunities, and future directions for developing NSD2 inhibitors and degraders are also discussed.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092389PMC
http://dx.doi.org/10.1021/acs.jmedchem.3c00948DOI Listing

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