MLN9708

MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. MLN9708 has a shorter proteasome dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared with bortezomib. MLN9708 has a larger blood volume distribution at steady state, and analysis of 20S proteasome inhibition and markers of the unfolded protein response confirmed that MLN9708 has greater pharmacodynamic effects in tissues than bortezomib. MLN9708 showed activity in both solid tumor and hematologic preclinical xenograft models. MLN9708 is current under phase II clinical trial in patients with relapsed multiple myeloma not refractory to bortezomib.