Products Cited in Publications Worldwide A clinical drug candidate that triggers non-apoptotic cancer cell death

A clinical drug candidate that triggers non-apoptotic cancer cell death

Dixon, Scott; Leak, Logan; Wang, Ziwei; Lee, Weaverly Colleen; Johnson, Brianna; Millner, Alec; Ko, Pin-Joe; Decosto, Cassandra; Magtanong, Leslie; Ritho, Joan

DOI: PMID:

Abstract

Small molecules that induce non-apoptotic 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 non-apoptotic 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 non-apoptotic cell death in response to CIL56 and tegavivint via the synthesis of the saturated long-chain fatty acid palmitate. These ndings outline a lipid-dependent non-apoptotic cell death mechanism that can be induced by a drug candidate currently being tested in humans.

Keywords

cancer ; TECR ; palmitate ; necrosis ; cancer

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(E)-Octadec-2-enoic acid

A14472652825-79-898%

(E)-Octadec-2-enoic acid

130.0/100mg

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