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Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month.
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RXDX-106
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CEP-40783
CAS No. : 1437321-24-8
MCE 国际站：CEP-40783
产品活性：CEP-40783是高效选择性，有口服活性的AXL和c-Met抑制剂，IC50值分别为7 nM 和12 nM。
研究领域：Protein Tyrosine Kinase/RTK
作用靶点：TAM Receptor | c-Met/HGFR
In Vitro: In AXL-transfected 293GT cells, CEP-40783 is 27-fold more active compared to recombinant enzyme with an IC50 value of 0.26 nM. CEP-40783 also demonstrates superior activity against c-Met in GTL-16 cells (IC50=6 nM). The increased inhibitory activity of CEP-40783 in cells could be attributed to its extended residence time on both AXL and c-Met, consistent with a Type II mechanism. CEP-40783 shows high kinome selectivity against 298 kinases with an S90 of 0.04 (fraction of kinases showing >90% inhibition at 1 µM).
In Vivo: CEP-40783 shows dose- and time-dependent inhibition of AXL phosphorylation using NCI-H1299 NSCL xenografts with 80% target inhibition at 0.3 mg/kg 6 h post dose and complete target inhibition to >90% inhibition at 1 mg/kg between 6-24 h, while a 10 mg/kg po dose resulted in complete AXL inhibition up to 48 h post dosing. In 3/5 (60%) of the tumor models, CEP-40783 shows in vivo efficacy, including tumor regressions, significantly superior to that achieved with an optimal regimen of paclitaxel. In 4/4 (100%) of the erlotinib-insensitive tumor models, CEP-40783 demonstrates significant efficacy (66 to 118% TGI) compared to the control group at the 30 mg/kg dose. Additionally, CEP-40783 in combination with erlotinib demonstrate superior anti-tumor efficacy compared to CEP-40783 and erlotinib single agents in the one erlotinib-sensitive model evaluated. CEP-40783 as a single agent and in combination with erlotinib are well tolerated.
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