MS170 is a highly effective and specific PROTAC AKT degrader compound that exhibits potent activity. It efficiently reduces the levels of total AKT (T-AKT) within cells, with a DC 50 value of 32 nM. Furthermore, MS170 demonstrates strong binding affinity towards AKT isoforms, specifically AKT1, AKT2, and AKT3, with respective dissociation constants (Kd) of 1.3 nM, 77 nM, and 6.5 nM.This compound is unstable in powder form and other related salt forms are recommended.

Akt3:6.5 nM (Kd), Akt2:77 nM (Kd), Akt1:1.3 nM (Kd)

Cereblon (CRBN)-recruiting degrader MS170 is a potent AKT degrader that demonstrates efficacy without exhibiting a hook effect. It selectively degrades AKT proteins, hindering downstream signaling and effectively inhibiting cancer cell growth. MS170 operates in a concentration- and time-dependent manner to degrade AKT via the ubiquitin-proteasome system (UPS)[1], and significantly inhibits proliferation across various cancer cell lines at concentrations ranging from 10 nM to 10 μM[1]. Specifically, MS170 depletes total AKT (T-AKT) with a DC50 value of 32±18 nM[1]. In cell proliferation assays using BT474, PC3, and MDA-MB-468 cells, MS170 exhibited growth inhibition with GI50s of 0.7±0.2 μM, 7.4±2.2 μM, and 5.7±2.4 μM, respectively, over a 5-day incubation period. Western blot analyses further corroborate these findings, showing potent AKT degradation in BT474 cells treated with MS170 across a broad range of concentrations for 24 hours.

MS170, administered through a single intraperitoneal (IP) injection at a dosage of 50 mg/kg, demonstrates bioavailability in male Swiss albino mice. Pharmacokinetic analysis reveals that the peak concentration (C max) reaches 1.4 μM at 2 hours post-administration, underscoring its effective distribution within the mouse model over an 8-hour period.