EGFR mutant-selective inhibitor BLU-945

A fourth-generation, orally bioavailable, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, EGFR mutant-selective inhibitor BLU-945 targets, binds to and inhibits the activity of EGFR with C797S triple mutations including ex19del/T790M/C797S and L858R/T790M/C797S, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. BLU-945 inhibits mutated forms of EGFR with C797S mutation, which prevents covalent bond formation with third-generation EGFR inhibitors leading to drug resistance. BLU-945 may have enhanced anti-tumor effects in tumors with C797S-mediated resistance when compared to other EGFR tyrosine kinase inhibitors.