| Name | CEP-40783 |
| Description | CEP-40783 (RXDX-106) is an effective, specific and orally active AXL/c-Met inhibitor (IC50: 7/12 nM). It also inhibits MER and TYRO3 (IC50: 29/19 nM). |
| In vitro | In AXL-transfected 293 gT cells, CEP-40783 is 27-fold more active compared to the recombinant enzyme (IC50: 0.26 nM). In GTL-16 cells, CEP-40783 also has superior activity against c-Met (IC50: 6 nM). The enhanced inhibitory activity of CEP-40783 in cells is attributed to its extended residence time on both c-Met and AXL, similar 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)[1]. |
| In vivo | CEP-40783 showed 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 AXL/NIH3T3 xenografts, 0.3 mg/kg po resulted in complete tumor regressions. CEP-40783 was also efficacious in reducing spontaneous lymph node and pulmonary metastatic tumor burden in the MDA-MB-231-luc and 4T1-luc orthotopic breast cancer models, respectively, at 10 and 30 mg/kg po. PK/PD evaluation of the c-Met activity of CEP-40783 (10, 30, 55 mg/kg po qdX5d) showed significant to complete inhibition of c-Met phosphorylation in GTL-16 gastric carcinoma xenografts. Efficacy studies in GTL-16 xenografts demonstrated significant anti-tumor efficacy (tumor stasis and regressions) at 10 and 30 mg/kg po. In EBC-1 NSCL xenografts, administration of CEP-40783 (3, 10 and 30 mg/kg, po qd) resulted in dose-related efficacy, with tumor stasis at 3 mg/kg, tumor regressions and >96% TGI at 10 mg/kg. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | H2O : Insoluble
Ethanol : 2 mg/mL (3.4 mM), Sonication is recommended.
DMSO : 5.89 mg/mL (10.01 mM), Sonication is recommended.
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| Keywords | Tyro3 | TAMReceptor | TAM Receptor | RXDX106 | RXDX 106 | Mer | Inhibitor | inhibit | HGFR | c-Met/HGFR | cMet/HGFR | c-MET | cMet | CEP-40783 | CEP40783 | AXL |
| Inhibitors Related | Bemcentinib | Gilteritinib | (S)-Afatinib | (Z)-Semaxinib | Decanoic Acid | Afatinib Dimaleate | L-Ascorbic acid 2-phosphate trisodium | Crizotinib | 7-Methoxy-1-tetralone | Tepotinib | Afatinib | Bacitracin Zinc |
| Related Compound Libraries | Reprogramming Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Tyrosine Kinase Inhibitor Library | Kinase Inhibitor Library | Drug Repurposing Compound Library | Inhibitor Library | Bioactive Compounds Library Max | Fluorochemical Library | Anti-Cancer Compound Library | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
