product name CNX-2006
Description: CNX-2006 is a novel, potent, irreversible mutant-selective EGFR inhibitor with IC50 of < 20 nM, with very weak inhibition at wild-type EGFR. CNX-2006 is the prototype for CO-1686, which is currently in a Phase I clinical trial for the treatment of EGFR-mutant lung cancer. In non-small cell lung cancer (NSCLC) models expressing mutant EGFR-T790M, CNX-2006 inhibited EGFR signaling.
References: Galvani E, Sun J, Leon LG, et al. Oncotarget, 2015.
545.53
Formula
C26H27F4N7O2
CAS No.
1375465-09-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (183.3 mM)
Water: <1 mg/mL
Ethanol: 29 mg/mL (53.1 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19416757
| In Vitro |
In vitro activity: CNX-2006 is a novel irreversible EGFR tyrosine kinase inhibitor, specifically inhibits activating mutations of EGFR as well as the T790M mutation while having very weak inhibition at wild-type EGFR. In in vitro modeling of acquired resistance, continuous CNX-2006 treatment on drug-sensitive EGFR mutant cells leads to resistance more slowly than erlotinib. Dose escalation with CNX-2006 leads to differential effects in different lines, but does not select for T790M-mediated resistance. CNX-2006 resistent cells shows increased expression of EMT markers and MMP9. Kinase Assay: Human EGFR mutant lung adenocarcinoma cell lines are treated with drugs in standard growth inhibition assays. Cell Assay: Cells with endogenous or transiently transfected mutant EGFRs (293 cells) are treated with inhibitors for 6 hours and then corresponding lysates are extracted and analyzed by immunoblotting. |
|---|---|
| In Vivo | CNX-2006 is effective in H1975 (EGFR L858R/T790M) xenograft model. |
| Animal model | Nude mice |
| Formulation & Dosage | 5% DMSO:15% Solutol HS15 in PBS; 25 mg/kg; i.p. |
| References |
