TAS 6417

TAS 6417 is a pan-EGFR inhibitor. It inhibits wild-type EGFR (IC50= 8 nM), as well as the EGFR point mutants EGFRL858R, EGFRL861Q, EGFRT790M, EGFRT790M/L858R (IC50s = 1.9, 5.5, 4.1, and 2 nM, respectively) and the insertion or deletion mutants EGFR D770_N771insNPG, EGFR d746-750, and EGFR d746-770/T790M (IC50s = 7.4, 1.4, and 1.1 nM, respectively). It is selective for these kinases over a panel of 20 additional kinases (IC50s = 44-850 nM) but does inhibit TXK, BMX, HER4, Tec, and BTK (IC50s = 1.1-22 nM). TAS 6417 inhibits the proliferation of LXF 2478L, H1975, HCC827, and PC-9 lung cancer cells (GI50s = 86.5, 45.4, 1.92, and 2.96 nM, respectively). In vivo, TAS 6417 (50, 100, and 200 mg/kg) reduces tumor volume and increases survival in an H1975 EGFR D770-N771insSVD mouse xenograft model.Formal Name: N-[(8S)-4-amino-8,9-dihydro-6-methyl-5-(3-quinolinyl)pyrimido[5,4-b]indolizin-8-yl]-2-propenamide. CAS Number: 1661854-97-2. Synonyms: CLN-081, Zipalertinib. Molecular Formula: C23H20N6O. Formula Weight: 396.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble. SMILES: CC1=C[C@H](NC(C=C)=O)CN2C1=C(C3=CN=C(C=CC=C4)C4=C3)C5=C2N=CN=C5N. InChi Code: InChI=1S/C23H20N6O/c1-3-18(30)28-16-8-13(2)21-19(15-9-14-6-4-5-7-17(14)25-10-15)20-22(24)26-12-27-23(20)29(21)11-16/h3-10,12,16H,1,11H2,2H3,(H,28,30)(H2,24,26,27)/t16-/m0/s1. InChi Key: MKCYPWYURWOKST-INIZCTEOSA-N.