(S)-JDQ-443 (C09-1141-007)

(S)-JDQ-443 is an isomer of JDQ-443 ( HY-139612 ). JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). JDQ-443 shows antitumor activity.In VitroJDQ-443 promotes dose-dependent reductions of phosphorylated ERK (pERK) levels and the proliferation of the KRASG12C-mutated cell lines NCI-H358 and NCI-H2122, with IC 50 values of 0.018 and 0.063 μM, respectively. JDQ443 covalently and selectively binds and inhibits GDP-bound KRASG12C with low reversible binding affinity to the RAS switch II pocket, and also inhibits proliferation of KRASG12C-mutated and KRAS G12C/H95, G12C/R68S, and G12C/Y96 double-mutant cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoJDQ443 (10-100 mg/kg, Orally, daily for 14 days) shows antitumor activity and inhibits the growth of tumor in a dose-dependent manner in KRAS G12C-mutated CDX models. JDQ443 (Orally, 100 mg/kg, daily (JDQ443) + 7.5 mg/kg, twice daily (TNO155), for 36 days) shows greater cell growth inhibition or cell killing compared with single-agent JDQ443 when combined with TNO155. JDQ443 generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid. Molecular Formula: C29H28ClN7O Molecular Weight: 526.03