MS143

MS143 is a potent AKT degrader (DC50=46 nM and GI50=0.8 µM in PC3 cells). MS143 induces rapid and robust AKT degradation in a concentration- and time-dependent manner via hijacking the ubiquitin-proteasome system. MS143 can suppress cancer cell growth[1].

Research Areas >> Cancer

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

AKT

MS143 (1 nM-10 μM; 24 hours) induces T-AKT degradation with a concentration-dependent manner in PC3 cells[1]. MS143 (0.1-10 µM;14 days, replenish every 2 days) effectively inhibits colony formation in BT474 cells[1]. MS143 (1 µM; 24 hours) promotes AKT degradation in an E3 ligase- and UPS-dependent manner[1]. MS143 (1 nM-10 µM) can inhibit the cell growth of PC3 cells (GI50=0.8 nM) and MDA-MB-468 cells (GI50=1.0 nM)[1]. Cell Proliferation Assay Cell Line: PC3 cells and MDA-MB-468 cells[1] Concentration: 1 nM, 10 nM, 100 nM, 1 μM, 10 μM Incubation Time: 5 days Result: Inhibited the cell growth of PC3 cells (GI50=0.8 nM) and MDA-MB-468 cells (GI50=1.0 nM). Western Blot Analysis Cell Line: PC3 cells[1] Concentration: 1 μM Incubation Time: 24 hours Result: Promoted AKT degradation in an E3 ligase- and UPS-dependent manner.

MS143 (75 mg/kg; i.p., 22 days) drastically inhibits the tumor growth by 92%, also substantially degrades T-AKT and P-AKT, and effectively inhibits the downstream signaling (PRAS40 phosphorylation) in xenograft mice[1]. Pharmacokinetic Parameters of MS143 in male Swiss Albino mice[1]. IP (75 mg/kg) Cmax (μM) 7 Tmax (h) 2 AUC0-12 (h·ng/mL) 63600 Animal Model: Male immunocompromised NU/J mice (6 weeks old)[1] Dosage: 75 mg/kg Administration: i.p., 22 days Result: Drastically inhibited the tumor growth by 92%, also substantially degraded T-AKT and P-AKT, and effectively inhibited the downstream signaling (PRAS40 phosphorylation).

[1]. Yu X, et al. Discovery of Potent, Selective, and In Vivo Efficacious AKT Kinase Protein Degraders via Structure-Activity Relationship Studies. J Med Chem. 2022;65(4):3644-3666.