TP421

TP421 (also known as Apoptosis Activator VIII) is a novel small molecule, mitochondriotropic triphenylphosphonium (TPP) salt that acts as an anticancer agent. Originally identified in a high-throughput screen at the University of Southern California, TP421 selectively accumulates in the mitochondria of cancer cells, driven by their elevated mitochondrial membrane potential. Mechanistically, it disrupts mitochondrial function, leading to decreased oxygen consumption, accumulation of reactive oxygen species (ROS), and G0/G1 cell cycle arrest. It triggers apoptosis via caspase activation and PARP-1 cleavage, inhibits autophagy (evidenced by LC3B-II and p62 accumulation), and suppresses cell migration by inhibiting Src-FAK signaling. Preclinical studies have demonstrated potent, sub-micromolar cytotoxicity against various pancreatic and breast cancer cell lines, as well as in vivo efficacy in mouse xenograft models.

Other names

(2-(7-(Diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)triphenylphosphonium bromideApoptosis Activator VIIITP-421TP421TP 421