M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical ( IC 50 =3.6 nM) and cellular ( IC 50 =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.
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