Antibiotic LL Z1640-2

Antibiotic LL Z1640-2 is a signal-specific inhibitor of the JNK/p38 pathways that has been shown to inhibit anisomycin-induced but not TNF-induced JNK/p38 activation. Shown to inhibit HgCl₂ and CdCl₂ MAPKs activation, while not affecting total protein level, in CCRF-CEM and NIH3T3 cells, respectively. Like other members of the resorcylic acid lactone (RAL) family, LL-Z1640-2 targets the ATP-binding pocket of kinases. Unlike other RALs, irreversibly inhibits TAK1. This cis-enone resorcylic acid lactone was first reported in 1978 and later rediscovered as an irreversible and highly selective TAK1 inhibitor. TAK1 is a MAPKKK involved in the p38 signalling cascade for pro-inflammation signals such as cytokines.