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ASK1 inhibitors block apoptosis signal-regulating kinase 1 (ASK1), a stress-activated kinase. ASK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the c-Jun N-terminal kinase (JNK) and p38 pathways. Sustained activation of these kinases by oxidative stress can drive apoptosis, inflammation and fibrosis. In resting cells, reduced thioredoxin binds ASK1 and keeps it inactive. Reactive oxygen species oxidize thioredoxin, which then releases ASK1 and allows the kinase to become active. ASK1 signaling is studied in models of liver fibrosis, kidney injury, neurodegeneration and cardiac remodeling. Selonsertib and GS-444217 compete with adenosine triphosphate (ATP) at the catalytic site of ASK1. TC ASK 10 and NQDI 1 are further inhibitors of the same kinase.
dASK1 is a selective PROTAC degrader targeting apoptosis signal-regulating kinase 1 (ASK1) through a cereblon (CRBN)-mediated pathway. This compound forms a stable ternary complex with ASK1, promoting its efficient degradation via the ubiquitin-proteasome system. dASK1 exhibits potent activity in degrading ASK1 and serves as a valuable tool in research focused on steatohepatitis and related pathologies.
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