CH6953755 is a potent, orally active and selective YES1 kinase (a member of the SRC family) inhibitor with an IC50 of 1.8 nM. CH6953755 inhibits YES1 kinase, leading to antitumor activity against YES1 Gene -amplified cancers in vitro and in vivo.
IC50&Target
IC50: 1.8 nM (YES1)
体外研究
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.
Cell Viability Assay
Cell 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 Analysis
Cell 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
体内研究
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.
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.
分子量
552.55
CAS号
2055918-71-1
运输条件
Room temperature in continental US; may vary elsewhere.