CEP-40783 is a robust, selective, and orally bioavailable antagonist of AXL and c-Met, exhibiting IC50 values of 7 nM and 12 nM, respectively. In cells transfected with AXL, such as 293GT, CEP-40783's activity is enhanced 27 times more than that of the recombinant enzyme, with an IC50 of 0.26 nM. Additionally, CEP-40783's efficacy against c-Met is pronounced in GTL-16 cells, with an IC50 of 6 nM. This heightened activity in cellular environments may be due to CEP-40783's prolonged binding to AXL and c-Met, aligning with a Type II mechanism. Furthermore, CEP-40783 is highly selective within the kinome, inhibiting over 90% of 298 kinases at a concentration of 1 µM, as indicated by an S90 value of 0.04[1].
CEP-40783 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Ba/F3 cells
100 nM
72 hours
Screening for drugs that inhibit MET D1228A/Y secondary mutations, CEP-40783 showed inhibitory effects
J Hematol Oncol. 2022 Jun 11;15(1):79.
Calu1
5 and 10 μM
72h
Evaluate the effect of RXDX106 on cell viability
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
Calu1
1 μM
4 hours
Evaluate the effect of RXDX106 on global phosphoproteins
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
Calu1
100 nM
30 min
Evaluate the inhibitory effect of RXDX106 on AXL phosphorylation
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
H1299
5 and 10 μM
72h
Evaluate the effect of RXDX106 on cell viability
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
H1299
1 μM
4 hours
Evaluate the effect of RXDX106 on global phosphoproteins
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
H1299
100 nM
30 min
Evaluate the inhibitory effect of RXDX106 on AXL phosphorylation
Mol Cancer Res. 2022 Apr 1;20(4):542-555.
CEP-40783 动物研究
Animal study
CEP-40783 demonstrates a dose-responsive and temporal inhibition of AXL phosphorylation in NCI-H1299 NSCL xenografts, achieving 80% inhibition at a dosage of 0.3 mg/kg six hours after administration. At a dosage of 1 mg/kg, it maintains >90% inhibition from 6 to 24 hours post-dose, and a 10 mg/kg oral dose sustains complete AXL inhibition for up to 48 hours post-dosing[1].
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