HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis

Abstract

Cell death: Blocking the self-destruct mechanism Researchers have identified a compound that inhibits necroptosis, a type of programmed cell death that occurs naturally but that can be harmful when overactivated. Necroptosis helps defend against disease, triggering virus-infected cells to self-destruct; however, hyperactivation of the mechanism is associated with inflammatory disorders such as inflammatory bowel disease. Triggering necroptosis requires a protein named RIP3, and Han-Hee Park at Ajou University, Suwon, South Korea and coworkers screened extensive chemical libraries to identify compounds that inhibit RIP3. They identified four compounds, and further testing showed that one, named HS-1371, strongly and specifically inhibited necroptosis in cells. HS-1371 could inhibit necroptosis even after the process had already begun, greatly broadening its therapeutic applications. HS-1371 may also help in treating other conditions that involve hyperactivation of necroptosis, including sepsis and multiple sclerosis.