LMP7-IN-1

M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC50=3.6 nM) and cellular (IC50=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells[1][2].

[1] Klein M, et al. Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) [published online ahead of print, 2021 Jul 6]. J Med Chem. 2021;10.1021/acs.jmedchem.1c00604. DOI:10.1021/acs.jmedchem.1c00604
[2] Sanderson MP, et al. M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models [published online ahead of print, 2021 May 27]. Mol Cancer Ther. 2021;10.1158/1535-7163.MCT-21-0005. DOI:10.1158/1535-7163.MCT-21-0005