m3258

M3258 is an orally bioavailable, potent, selective, and reversible small molecule inhibitor of the large multifunctional peptidase 7 (LMP7; also known as Beta5i or PSMB8), a chymotrypsin-like proteolytic subunit of the immunoproteasome. The drug was developed to specifically target and inhibit LMP7 activity in hematopoietic cells such as those found in multiple myeloma. By blocking LMP7’s proteolytic function within the immunoproteasome—while sparing other proteasome subunits—M3258 disrupts protein degradation pathways essential for tumor cell survival. This leads to accumulation of polyubiquitinated proteins and induction of apoptosis in malignant cells. Preclinical studies demonstrated strong antitumor efficacy in multiple myeloma xenograft models with high selectivity for LMP7 over other proteasomal subunits[1][2][3][4][5][7]. A phase I clinical trial was initiated for relapsed/refractory multiple myeloma[5][6][7]. M3258 was discovered and developed by Merck KGaA[7][8].

Other names

((1R)-2-(1-benzofuran-3-yl)-1-(((1S,2R,4R)-7-oxabicyclo(2.2.1)heptane-2-carbonyl)amino)ethyl)boronic acidCHEMBL5184466CHEMBL-5184466CHEMBL 5184466