Conteltinib (C09-1121-074)

Conteltinib (CT-707) is a multi-kinase inhibitor targeting FAK , ALK, and Pyk2 . Conteltinib exerts significant inhibitory effect on FAK with an IC 50 of 1.6 nMIn VitroConteltinib (CT-707) synergizes with XL184 to suppress hepatocellular carcinoma by blocking XL184-induced FAK activation. ?/nThe combination of XL184 (5 μM) and Conteltinib (3 μM) significantly reduces the survival fraction, compared with each agent alone. ?/nThe combination of XL184 (5 μM) and Conteltinib (3 μM) results in enhanced caspase-dependent apoptosis in human hepatocellular carcinoma cell lines. ?/nThe FAK phosphorylation induced by XL184 (5 μM) might be involved in the synergistic antitumor effect of Conteltinib (3 μM) and XL184. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: The human hepatocellular carcinoma cell lines HepG2 and Bel-7402 Concentration: 1.0, 1.5, 2.0, 2.5, and 3.0 μM for HepG2 cells; 0.2, 0.4, 0.8, 1.5, and 3.0 μM for Bel-7402 cells Incubation Time: 72 hours Result: When cells were exposed to XL184 (5 μM), Conteltinib (3 μM), or their combination, the survival rates were 57.3%, 39.3%, and 11.2%, respectively, in HepG2; those in Bel-7402 were 57.8%, 61.6%, and 34.2%, respectively. Apoptosis AnalysisCell Line: HepG2 and Bel-7402 cells Concentration: 3 μM Incubation Time: 48 hours Result: The apoptosis rates of control, XL184, Conteltinib, and combination groups in HepG2 were 5.0%, 10.5%, 18.4%, and 41.1%, respectively, and those in Bel-7402 were 4.4%, 16.3%, 8.7%, and 36.4%, respectively. Western Blot AnalysisCell Line: HepG2 and Bel-7402 Concentration: 3 μM Incubation Time: 24 hours Result: Could markedly decrease FAK phosphorylation induced by XL184, which might partially account for the synergetic effect.In VivoThe combination of XL184? (20 mg/kg once daily for first 3 days; i.g. 10 mg/kg once a day for 4th day; no administration from 5th to 10th days; i.g. 10 mg/kg once a day from the 10th to 14th days )and CT-707? (i.g. 50 mg/kg twice a day for first 3 days, 7th, 8th, 11th, 12th, and 14th days; once a day for 4th, 6th, 9th, 10th, and 13th days; no administration for the 5th day) shows? the synergistic antitumor effect in HepG2 xenograft nude mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Nude mice transplanted with HepG2 xenografts Dosage: 50 mg/kg Administration: Intragastrically (i.g.) twice a day for first 3 days, 7th, 8th, 11th, 12th, and 14th days; once a day for 4th, 6th, 9th, 10th, and 13th days; no administration for the 5th day. Result: Caused a moderate decrease in the relative tumor volume (RTV). The inhibition rate of combination group reached 77.4%, whereas the mono-treatment of XL184 or CT-707 alone caused 30.7% and 19.4% inhibition in the tumor weight, respectively.IC50& Target:IC50: 1.6 nM (FAK). Specification: 10mM in DMSO Molecular Formula: C32H45N9O3S Molecular Weight: 635.82