RGNCY-0089 (TAS6417 EGFR Inhibitor)

TAS6417 is a novel EGFR (epiderrmal growth factor receptor) inhibitor that targets EGFR exon 20 insertion mutations while sparing wild type EGFR.  Non-small-cell lung carcinoma (NSCLC) driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose limiting toxicity and so new therapies are required.  TAS6417 inhibits EGFR phosphorylation (IC50 =1.1 + 0.1 to 0.8 + 1.1 nmol/L) and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions which results in caspase activation.  This results in significant tumor regression in vivo in both genetically engineered model and patient derived xenograft model.  TAS6417 demonstrates a survival benefit with marked tolerability in a lung orthotopic implantation mouse model.  TAS6417 is a promising and efficacious drug candidate for NSCLC patients carrying exon 20 insertion mutations.

Systematic Name:  (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide

SMILES:  NC1=C2C(N(C[C@@H](NC(C=C)=O)C=C3C)C3=C2C4=CC(C=CC=C5)=C5N=C4)=NC=N1

Formula:  C23H20N6O

Mol Wt:  396.17

PMID:  29748209