CL-387785

CL-387785 (also known as EKI-785) is an irreversible, small-molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Originally developed to target EGFR mutations, it is characterized as a third-generation inhibitor in recent literature due to its ability to overcome certain resistance mechanisms. Beyond its primary role as a kinase inhibitor, CL-387785 has been shown to induce necroptosis—a form of immunogenic cell death—in melanoma and lung cancer cells. This effect is mediated by the targeting of the tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD), which recruits RIPK1 and triggers the NF-κB signaling pathway. This cascade leads to the upregulation of CD80 on the tumor cell surface, enhancing CD8+ T lymphocyte activity and effectively sensitizing tumors to immune checkpoint therapies, such as anti-PD-1 antibodies.

Other names

N-[4-(3-bromoanilino)quinazolin-6-yl]but-2-ynamide