LCL124

LCL124 is a cationic analog of ceramide designed to selectively induce apoptosis in pancreatic cancer cells by targeting mitochondria based on their more negative mitochondrial membrane potential. Mechanistically, LCL124 accumulates in cancer cell mitochondria, resulting in mitochondrial depolarization, cytochrome c release, caspase activation (caspase-3/7), and PARP cleavage, ultimately inducing apoptosis. Importantly, LCL124 displays a significant therapeutic window, being substantially more active in cancer cells than in nonmalignant pancreatic cells. In vivo, LCL124 inhibits the growth of pancreatic cancer xenografts and improves animal survival, with potential to circumvent gemcitabine resistance.

Other names

(2S,3S,4E)-2-N-[6'-(1″-pyridinium)-hexanoyl-sphingosine bromide)cationic ceramide analog