CH6953755 is a potent, orally active and selective YES1 kinase (a member of the SRC family) inhibitor with an IC 50 of 1.8 nM. CH6953755 inhibits YES1 kinase, leading to antitumor activity against YES1 Gene -amplified cancers in vitro and in vivo
In Vitro
CH6953755 (0.001-1 μM; for 4 days) inhibits the cell growth of YES1-amplified cancer cell lines. CH6953755 (0.001-1 μM; for 2 hours) prevents the autophosphorylation at Tyr426 of YES1 that upregulates enzymatic activity in KYSE70 cells harboring YES1 amplification. CH6953755 (0.1, 0.3, 1, 3 μM) suppresses TEAD luciferase reporter activity in YES1-amplified KYSE70 and RERF-LC-AI. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: YES1-amplified cancer cell lines KYSE70 and OACP4 C, and non-YES1–amplified cancer cell line K562 expressing YES1-WT or YES1-GK Concentration: 0.001, 0.01, 0.1, 1 μM Incubation Time: 4 days Result: Inhibited the cell growth of YES1-amplified cancer cell lines. Western Blot AnalysisCell Line: KYSE70 cell line Concentration: 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1 μM Incubation Time: 2 hours Result: Prevented the autophosphorylation at Tyr426 of YES1 that upregulates enzymatic activity in KYSE70 cells harboring YES1 amplification
In Vivo
CH6953755 (oral; 60 mg/kg/day; for 10 days) shows selective antitumor activity accompanied with phospho-Tyr426 YES1 suppression in xenograft tumors . CH6953755 (oral; 7.5, 15, 30, 60 mg/kg) suppresses phospho-Tyr426 YES1 in a dose-dependent manner . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female BALB/c-nu/nu mice with Rat-2_YES1 xenograft Dosage: 60 mg/kg Administration: Oral; daily; for 10 days Result: Showed selective antitumor activity accompanied with phospho-Tyr426 YES1 suppression in xenograft tumors.
IC50& Target:IC50: 1.8 nM (YES1)
