MS432 is a first-in-class and highly selective PD0325901-based von Hippel-Lindau -recruiting PROTAC degrader for MEK1 and MEK2 . MS432 displays good plasma exposure in mice, exhibiting DC 50 values of 31 nM and 17 nM for MEK1 , MEK2 in HT29 cells respectively
In Vitro
MS432 (compound 23) is potent in reducing MEK1/2 protein levels in COLO 205 cells (DC 50 (MEK1) = 18 ± 7 nM, DC 50 (MEK2) = 11 ± 2 nM) and UACC257 cells (DC 50 (MEK1) = 56 ± 25 nM, DC 50 (MEK2) = 27 ± 19 nM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: (HT-29, SK-MEL-28, COLO 205 and UACC 257 cell lines. Concentration: 0-1 μM. Incubation Time: 72 hours. Result: Effectively inhibited proliferation of these CRC and melanoma cells in a concentration-dependent manner, with GI 50 values ranging from 30 to 200 nM.
In Vivo
MS432 (compound 23) displays good plasma exposure, which is approximately 3 to 20-fold higher than the GI 50 values of compound 23 in the tested cancer cell lines . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Swiss Albino mice . Dosage: 50 mg/kg (Pharmacokinetic Analysis). Administration: IP Result: Displays good plasma exposure with the maximum plasma concentration of 1,400 nM detected at 0.5 hour post dosing and plasma concentration of 710 nM at 8 hours post dosing.
Form:Solid
IC50& Target:MEK1 31 nM (DC 50 , in HT29 cells) MEK2 17 nM (DC 50 , in HT29 cells) MEK1 31 nM (DC 50 , in SK-MEL-28 cells) MEK2 9.3 nM (DC 50 , in SK-MEL-28 cells)
| Solubilità | DMSO : 260 mg/mL (241.62 mM; Need ultrasonic) |
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