1437321-24-8
1437321-24-8 structure
- Name: CEP-40783
- Chemical Name: CEP-40783
- CAS Number: 1437321-24-8
- Molecular Formula: C31H26F2N4O6
- Molecular Weight: 588.558
- Catalog: Signaling Pathways Protein Tyrosine Kinase/RTK c-Met/HGFR
- Create Date: 2018-06-28 22:40:31
- Modify Date: 2024-01-02 14:58:27
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CEP-40783 is a potent, selective and orally available inhibitor of AXL and c-Met with IC50 values of 7 nM and 12 nM, respectively.
| Name | CEP-40783 |
|---|---|
| Synonyms |
N-{4-[(6,7-Dimethoxy-4-quinolinyl)oxy]-3-fluorophenyl}-3-(4-fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide
5-Pyrimidinecarboxamide, N-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-1,2,3,4-tetrahydro-1-(1-methylethyl)-2,4-dioxo- |
| Description | CEP-40783 is a potent, selective and orally available inhibitor of AXL and c-Met with IC50 values of 7 nM and 12 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 7 nM (AXL) and 12 nM (c-Met)[1] |
| 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)[1]. |
| 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[1]. 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[2]. |
| Animal Admin | Mice: Mice bearing established Champions TumorGrafts are treated orally with 10 mg/kg and 30 mg/kg qd of CEP-40783 for 10 to 34 days and anti-tumor efficacy and tolerability are evaluated[2]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C31H26F2N4O6 |
| Molecular Weight | 588.558 |
| Exact Mass | 588.182068 |
| LogP | 5.35 |
| Index of Refraction | 1.646 |
| Storage condition | -20℃ |