Products Cited in Publications Worldwide Tegavivint triggers TECR-dependent nonapoptotic cancer cell death

Tegavivint triggers TECR-dependent nonapoptotic cancer cell death

Leak, Logan; Wang, Ziwei; Joseph, Alby J; Johnson, Brianna; Chan, Alyssa A; Decosto, Cassandra M; Magtanong, Leslie; Ko, Pin-Joe; Lee, Weaverly Colleen; Ritho, Joan

DOI: PMID:

Abstract

Small molecules that induce nonapoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of nonapoptotic cell death in sarcomas and other cancer cells. This lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR). TECR is canonically involved in the synthesis of very-long-chain fatty acids but appears to promote nonapoptotic cell death in response to CIL56 and tegavivint via the synthesis of the saturated long-chain fatty acid palmitate. These findings outline a lipid-dependent nonapoptotic cell death mechanism that can be induced by a drug candidate currently being tested in humans.

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(E)-Octadec-2-enoic acid

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