CNX-2006

CNX-2006 is an irreversible inhibitor of mutant EGFRs. It inhibits EGFR phosphorylation in PC-9 and HCC827 cells (IC50s = 55-104 nM), which express the EGFRDel E746_A750 mutation, and NCI H1975 and PC-9/GR4 cells (IC50s = 46 and 61 nM, respectively), which express the EGFRL858R/T790M and EGFRDel E746_A750/T790M mutations, respectively. It is greater than 10-fold selective for cells expressing these mutants over A549 cells expressing wild-type EGFR. CNX-2006 inhibits growth in a panel of non-small cell lung cancer (NSCLC) cells expressing wild-type or mutant EGFRs (GI50s = 0.34-8 and 0.003-3.6 µM, respectively). It reduces tumor growth in an NCI H1975 mouse xenograft model when administered at doses of 25 and 50 mg/kg.Formal Name: N-[3-[[2-[[4-[[1-(2-fluoroethyl)-3-azetidinyl]amino]-2-methoxyphenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]phenyl]-2-propenamide. CAS Number: 1375465-09-0. Molecular Formula: C26H27F4N7O2. Formula Weight: 545.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml, Ethanol: 10 mg/ml. lambdamax: 276 nm. SMILES: O=C(C=C)NC1=CC=CC(NC2=C(C(F)(F)F)C=NC(NC3=CC=C(NC4CN(CCF)C4)C=C3OC)=N2)=C1. InChi Code: InChI=1S/C26H27F4N7O2/c1-3-23(38)33-16-5-4-6-17(11-16)34-24-20(26(28,29)30)13-31-25(36-24)35-21-8-7-18(12-22(21)39-2)32-19-14-37(15-19)10-9-27/h3-8,11-13,19,32H,1,9-10,14-15H2,2H3,(H,33,38)(H2,31,34,35,36). InChi Key: BFSRTTWIPACGMI-UHFFFAOYSA-N.