EAI045

• CAT Number: I013761
• CAS Number: 1942114-09-1
• Molecular Formula: C39H14FN3O3S
• Molecular Weight: 383.4
• Purity: ≥95%
• Target: EGFR
• Solubility: DMSO: ≥ 28 mg/mL
• IUPAC Name: 2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide
• InChI: InChI=1S/C19H14FN3O3S/c20-12-5-6-15(24)14(9-12)16(17(25)22-19-21-7-8-27-19)23-10-11-3-1-2-4-13(11)18(23)26/h1-9,16,24H,10H2,(H,21,22,25)
• InChIKey: YTUFHOKUFOQRDF-UHFFFAOYSA-N
• SMILES: C1C2=CC=CC=C2C(=O)N1C(C3=C(C=CC(=C3)F)O)C(=O)NC4=NC=CS4

EAI045 (CAT: I013761) is an allosteric inhibitor specifically designed to target certain drug-resistant mutants of the epidermal growth factor receptor (EGFR). It is effective against EGFR mutations such as T790M, which are commonly associated with resistance to EGFR-targeted therapies in non-small cell lung cancer (NSCLC) patients. By binding to the allosteric site of the mutant EGFR, EAI045 inhibits the signaling pathways involved in cancer cell growth and survival. This targeted inhibition offers a potential therapeutic strategy for overcoming resistance to EGFR inhibitors and improving treatment outcomes in patients with drug-resistant EGFR mutations.

Reference

1:Cancer Lett. 2017 Jan 28;385:51-54. doi: 10.1016/j.canlet.2016.11.008. Epub 2016 Nov 10. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance.Wang S,Song Y,Liu D, PMID: 27840244 DOI: 10.1016/j.canlet.2016.11.008 Abstract: The third-generation tyrosine kinase inhibitors (TKI), AZD9291 (osimertinib) and CO-1686 (rociletinib) of epidermal growth factor receptor (EGFR) are highly active against T790M positive non-small cell lung cancer (NSCLC). However, resistance develops rapidly. EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third-generation inhibitors. This review summarizes the latest development on the discovery of a fourth-generation EGFR TKI, EAI045.3.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.