MS98 is a highly effective and specific PROTAC AKT degrader compound that effectively targets and depletes total AKT (T-AKT) within cells, exhibiting a DC 50 value of 78 nM. This compound readily binds to AKT1, AKT2, and AKT3 with respective dissociation constants (Kd s) of 4 nM, 140 nM, and 8.1 nM.

Akt3:8.1 nM, Akt1:4 nM, Akt2:140 nM

The VHL-recruiting degrader MS98 is a potent AKT degrader that induces AKT protein degradation and inhibits downstream signaling pathways, thereby suppressing cancer cell proliferation. Utilizing the ubiquitin-proteasome system (UPS), MS98 achieves concentration- and time-dependent AKT degradation. Specifically, at concentrations of 10 nM to 10 μM, MS98 significantly inhibits proliferation across various cancer cell lines and depletes cellular total AKT (T-AKT) with a DC50 of 78±64 nM. Cell viability assays show MS98 inhibits growth in BT474, PC3, and MDA-MB-468 cells with GI50 values of 1.3±0.3 μM, 9.2±1.3 μM, and 3.8±1.2 μM, respectively. Western Blot analysis of BT474 cells with MS98 (1 nM to 10 μM over 24 hours) demonstrates potent AKT degradation, confirming its efficacy in inhibiting cancer cell growth.

MS98, administered through a single intraperitoneal (IP) injection at a dosage of 50 mg/kg, exhibits bioavailability in male Swiss albino mice. Pharmacokinetic analysis reveals that the maximum plasma concentration (C max) of approximately 3.5 μM is achieved 2 hours post-injection, with plasma levels remaining above 3 μM for a duration of over 8 hours.