LL-Z-1640-2

LL Z1640-2 is a cis-enone resorcylic acid lactone first reported in 1978 and later rediscovered as an irreversible and highly selective TAK 1 inhibitor. TAK1 is a MAPKKK involved in the p38 signalling cascade for pro-inflammation signals such as cytokines. LL Z1640-2 effectively prevents inflammation in animal models.

Resorcyclic lactone of fungal origin that acts as a potent and selective transforming growth factor- β -activated kinase 1 (TAK1) mitogen-activated protein kinase kinase kinase (MAPKKK) inhibitor (IC 50 = 8 nM). Displays > 33-fold and > 62-fold selectivity over MEKK1 and MEKK4 respectively. Inhibits IL-1-induced activation of NF- κ B (IC 50 = 83 nM) and JNK/p38. Inhibits production of inflammatory mediators, and sensitizes cells to TRAIL- and TNF- α -induced apoptosis in vitro .