CEP-40783 (RXDX-106) is a potent, selective and orally available inhibitor of AXL and c-Met with IC50 values of 7 nM and 12 nM, respectively. 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.
|Cell lines||3T3 cells|
|Preparation method||3T3 cells expressing Tyro3, Axl, or Mer are incubated with vehicle alone or CEP-40783 for 30 minutes, and receptor phosphorylation is monitored.|
|Concentrations||0.25, 1, 2.5, 10, 25, 100, 250 nM|
|Incubation time||30 min|
|Animal models||SCID Beige mice|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO 8 mg/mL|
|Related c-Met Products|
Bozitinib (PLB-1001; CBT-101) is a highly selective, blood-brain barrier permeable c-MET kinase inhibitor.
Glumetinib, also known as SCC244, is a novel, potent and highly selective inhibitor of c-Met with an IC50 of 0.42 nM.
NPS-1034 is a dual inhibitor of Axl and MET with IC50 values of 10.3 and 48 nM, respectively.
Savolitinib (volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase.
AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.