MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC 50 value of 32 nM. MS170 binds to AKT1 , AKT2 , and AKT3 with K d s of 1.3 nM, 77 nM, and 6.5 nM, respectively
In Vitro
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). MS170 (10 nM-10 μM) effectively inhibits the proliferation in multiple cancer cell lines. MS170 (1 nM-10 μM) concentration-dependently depletes cellular total AKT (T-AKT) with the DC 50 value of 32±18 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell 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 0.7±0.2 μM, 7.4±2.2 μM, and 5.7±2.4 μM for BT474 cells, PC3 cells, and MDA-MB-468 cells, respectively. Western Blot AnalysisCell 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.
In Vivo
MS170 (a single intraperitoneal injection at a dose of 50 mg/kg) is bioavailable in mice via IP injection . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Swiss albino mice Dosage: Single 50 mg/kg(Pharmacokinetic Analysis) Administration: IP injection over 8 h Result: Bioavailable in mouse PK studies. The C max is1.4 μM at 2 h.
Form:Solid
IC50& Target:Akt1 1.3 nM (Kd) Akt2 77 nM (Kd) Akt3 6.5 nM (Kd) CRBN-DDB1
