NSD2i-1

NSD2i-1 is a first-in-class, highly selective small molecule inhibitor of the histone lysine methyltransferase NSD2 (also known as MMSET/WHSC1), designed as a catalytic inhibitor that blocks NSD2-mediated dimethylation of histone H3 lysine 36 (H3K36me2) and thereby rewires chromatin accessibility and gene expression programs in cancer cells.[5][9][10] Preclinical studies with NSD2 inhibitor chemotypes (collectively referred to as NSD2i) demonstrate single-digit nanomolar potency on NSD2, strong selectivity over related methyltransferases, reversal of H3K36me2-driven chromatin plasticity, restoration of H3K27me3-mediated repression at oncogenic loci, and broad antitumor activity in KRAS-driven lung and pancreatic models, as well as in multiple myeloma models with t(4;14) translocations.[5][6][8][9] NSD2i-1 has been described in the literature as a prototype clinical-grade NSD2 inhibitor used to validate NSD2 as a therapeutic target rather than as a fully characterized development candidate, and it is positioned mechanistically as an epigenetic modulator that may synergize with targeted agents such as KRAS G12C inhibitors or androgen receptor pathway inhibitors by reversing lineage plasticity and drug resistance.[3][5]

Other names

NSD2 inhibitor-1NSD-2 inhibitor-1NSD 2 inhibitor-1NSD2iNSD-2iNSD 2i