LCL-461

LCL-461 is a mitochondria-targeted ceramide analogue designed to selectively induce mitophagy in cancer cells. Developed primarily at the Medical University of South Carolina, the compound consists of a C6-ceramide backbone conjugated to a positively charged pyridinium group. This modification allows the molecule to accumulate preferentially within the negatively charged mitochondrial matrix. Once localized to the mitochondria, LCL-461 facilitates the recruitment of LC3B-II to the mitochondrial outer membrane, thereby triggering the autophagic degradation of the mitochondria (mitophagy). In the context of Acute Myeloid Leukemia (AML), LCL-461 has been shown to induce mitophagy-dependent cell death and can modulate the cellular response to ferroptosis, making it a candidate for combination therapies targeting mitochondrial quality control mechanisms.

Other names

C6-pyridinium-ceramideC-6-pyridinium-ceramideC 6-pyridinium-ceramidemitochondria-targeted ceramide