| Hazard Information | Back Directory | [Uses]
MS143 is a potent PROTAC 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 (Pink: AKT ligand (HY-15431); Blue: E3 ligase ligand (HY-125845); Black: linker)[1]. | [in vivo]
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). |
| [References]
[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. DOI:10.1021/acs.jmedchem.1c02165 |
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