EAI045 CAS No.1942114-09-1

EAI045 is a potent and selective inhibitor of mutant EGF receptors (EGFRs; IC50s = 0.076, 0.049, 0.002, and 1.6 μM for recombinant EGFRL858R, EGFRT790M, EGFRL858R/T790M, and wild-type EGFR, respectively). It inhibits phosphorylation of EGFR in a concentration-dependent manner in H1975 cells. EAI045 (0.01-10 μM) reduces proliferation of Ba/F3 cells expressing EGFRL858R/T790Mand EGFRL858R/T790M/I941R.In vivo, EAI045 induces tumor regression and reduces EGFR signaling in mice bearing EGFRL858R/T790M, EGFRExon19del/T790M, and EGFRL858R/T790M/C797Stumors when administered at a dose of 60 mg/kg per day in combination with cetuximab.
EAI045 is a potent and selective EGFR inhibitor (fourth generation). EAI045 targets selected drug-resistant EGFR mutants without affecting the wild-type receptor. EAI045 inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. Therefore, it is a potential candidate drug for the treatment of related non-small cell lung cancer (NSCLC). It should be noted that EAI-045 is effectively in targeting the EGFR C797S mutation, which is resistance to the third-generation EGFR inhibitors including AZD9291 (osimertinib) and CO-1686 (rociletinib).