The von Hippel-Lindau (VHL)-recruiting degrader MS98 is an effective AKT degrader. MS98 selectively induces robust AKT protein degradation, inhibits downstream signaling, and suppresses cancer cell proliferation. MS98 concentration- and time-dependently induces AKT degradation through the ubiquitin-proteasome system (UPS)[1]. MS98 (10 nM-10 μM) effectively inhibits the proliferation in multiple cancer cell lines[1]. MS98 (1 nM-10 μM) concentration-dependently depletes cellular total AKT (T-AKT) with the DC 50 value of 78±64 nM[1]. Cell Viability Assay[1]Cell Line: BT474, PC3, and MDA-MB-468 cells Concentration: 10 nM, 100 nM, 1 μM, 10 μM Incubation Time: 5 days Result: Inhibited the cell growth with GI 50 s of 1.3±0.3 μM, 9.2±1.3 μM, and 3.8±1.2 μM for BT474 cells, PC3 cells, and MDA-MB-468 cells, respectively. Western Blot Analysis[1]Cell Line: BT474 cells Concentration: 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM, 1 μM , 3 μM, and 10 μM Incubation Time: 24 hours Result: Potently induced AKT degradation.

MS98 (a single intraperitoneal injection at a dose of 50 mg/kg) is bioavailable in mice via IP injection. The maximum plasma concentration (C max ) reaches approximately 3.5 μM at 2 h, and the plasma concentrations remains above 3 μM over 8 h[1]. Animal Model: Male Swiss albino mice[1]Dosage: Single 50 mg/kg(Pharmacokinetic Analysis) Administration: IP injection over 8 h Result: Bioavailable in mouse PK studies. The C max is 3.5 μM at 2 h.