EGFR-IN-1 TFA

• CAT Number: I045783
• CAS Number: 2753348-63-7
• Molecular Formula: C30H31F3N6O6
• Molecular Weight: 628.60
• Purity: ≥95%
• Synonyms: N-[3-[2-[4-[2-(dimethylamino)ethoxy]-2-methoxyanilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]phenyl]prop-2-enamide;2,2,2-trifluoroacetic acid
• InChI: InChI=1S/C28H30N6O4.C2HF3O2/c1-6-25(35)30-19-8-7-9-20(15-19)34-26(36)14-18(2)22-17-29-28(32-27(22)34)31-23-11-10-21(16-24(23)37-5)38-13-12-33(3)4;3-2(4,5)1(6)7/h6-11,14-17H,1,12-13H2,2-5H3,(H,30,35)(H,29,31,32);(H,6,7)
• InChIKey: YXUXRIRLHPSVTF-UHFFFAOYSA-N
• SMILES: CC1=CC(=O)N(C2=NC(=NC=C12)NC3=C(C=C(C=C3)OCCN(C)C)OC)C4=CC=CC(=C4)NC(=O)C=C.C(=O)(C(F)(F)F)O

EGFR-IN-1 TFA is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. EGFR-IN-1 TFA potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 TFA displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity[1].
EGFR-IN-1 TFA (compound 24) is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. EGFR-IN-1 TFA potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 TFA displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity[1].
EGFR-IN-1 TFA (30 mg/kg; p.o.; daily for 2 weeks) displays significant tumor growth inhibition with no observed loss in body weight[1].
EGFR-IN-1 TFA evaluates in a time course PD experiment upon oral dosing at 30 mg/kg. EGFR-IN-1 TFA shows a >50% inhibition of phosphorylation of EGFR for >12 h. EGFR-IN-1 TFA reaches maximal concentration of 0.10 μM at 2 h and systemic exposure (AUC0-inf.) is 0.33 μM. h[1].

Reference

[1]. Wurz RP, et al. Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors. ACS Med Chem Lett. 2015 Jul 27;6(9):987-92.
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