MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC50 value of 32 nM. MS170 binds to AKT1, AKT2, and AKT3 with Kds of 1.3 nM, 77 nM, and 6.5 nM, respectively[1].
Cereblon (CRBN)-recruiting degrader MS170 is an effective AKT degrader without a ″hook effect″. MS170 selectively induces robust AKT protein degradation, inhibits downstream signaling, and suppresses cancer cell proliferation. MS170 concentration- and time-dependently induces AKT degradation through the ubiquitin-proteasome system (UPS)[1]. MS170 (10 nM-10 μM) effectively inhibits the proliferation in multiple cancer cell lines[1]. MS170 (1 nM-10 μM) concentration-dependently depletes cellular total AKT (T-AKT) with the DC50 value of 32±18 nM[1].
MS170 (a single intraperitoneal injection at a dose of 50 mg/kg) is bioavailable in mice via IP injection[1].
[1]. Yu X, et al. Design, Synthesis, and Evaluation of Potent, Selective, and Bioavailable AKT Kinase Degraders. J Med Chem. 2021;64(24):18054-18081.