Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications[1].

Kongensin A (0-15 μM; 6 hours; HT29 cells) treatment induces caspase activation and apoptosis in multiple cancer cell lines in a dosage-dependent manner[1].Kongensin A (0-15 μM; 24 hours; HT29 cells) treatment induces the degradation of RIPK1 and oncogenic kinases such as ERBB2, AKT, EGFR, and B-raf, and induces the up-regulation of HSP90A and HSP90B[1].Kongensin A covalently binds to cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its cochaperone CDC37. The HSP90-CDC37 complex is required for RIP3 activation, KA blocks LPS/Smac mimetics/Z-VAD and RIP3 polymerization-induced cell death, in which cell death is dependent on RIP3 but not its upstream kinase RIP1[1].

[1]. Li D, et al. Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis. Cell Chem Biol. 2016 Feb 18;23(2):257-266.