AZ14289671

AZ14289671 is an orally bioavailable, potent, and irreversible small molecule tyrosine kinase inhibitor (TKI) specifically designed to target epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Developed by AstraZeneca, it is characterized by its high selectivity for exon 20 insertions over wild-type EGFR, which potentially reduces off-target toxicities such as skin rash and diarrhea. Notably, the compound is blood-brain barrier penetrant, making it a promising candidate for treating non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastases, a population with significant unmet medical need. Preclinical data indicates significant signaling inhibition and sustained tumor regression across various exon 20 insertion models.