MS170

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].

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Signaling Pathways >> PROTAC >> PROTAC

Akt1:1.3 nM (Kd)

Akt2:77 nM (Kd)

Akt3:6.5 nM (Kd)

CRBN-DDB1

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]. Cell Proliferation 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 GI50s 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 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.

MS170 (a single intraperitoneal injection at a dose of 50 mg/kg) is bioavailable in mice via IP injection[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 Cmax is1.4 μM at 2 h.

[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.