M3258 (M 3258) is a potent, reversible, highly selective and orally acitve LMP7 inhibitor with cellular IC50 of 4.1 nM.
M3258 does not inhibit other constitutive proteasome and immunoproteasome subunits (IC50>2.5 uM).
M3258 demonstrated strong antitumor efficacy in multiple myeloma xenograft models.
M3258 treatment led to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells both in vitro and in vivo.
M3258 showed superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib.
