Nuclear receptor binding SET domain protein 2 (NSD2)

Nuclear receptor binding SET domain protein 2 (NSD2) is an epigenetic enzyme that catalyzes the mono- and dimethylation of lysine 36 on histone H3 (H3K36me1 and H3K36me2) using S-adenosylmethionine as a methyl donor. NSD2 plays a crucial role in chromatin modification, gene regulation, and development. Overexpression or mutation of NSD2 is implicated in various malignancies, especially multiple myeloma with t(4;14) translocation and other cancers, due to its promotion of cell proliferation and alteration of gene expression profiles. Beyond its canonical histone substrates, NSD2 can also methylate additional histone marks and participates in DNA damage repair. Given its central role in disease processes and amenability to small-molecule inhibition, NSD2 is a key therapeutic target in oncology drug development, with several inhibitors under preclinical and clinical evaluation.

Other names

MMSETWHSC1TRX5REIIBPKMT3GWolf-Hirschhorn syndrome candidate 1

Inhibition of NSD2 methyltransferase activity, Blockade of H3K36 methylation, Disruption of chromatin regulation and oncogenic transcription