Receptor-interacting serine/threonine protein kinase 3 (RIPK3 or RIP3) activation following the induction of necroptosis in human HT-29 colorectal adenocarcinoma cells requires the activity of a heat-shock protein 90 (HSP90) and cell division cycle 37 (CDC37) cochaperone complex (Li D et al. 2015). This complex physically associates with RIPK3. Chemical inhibitors of HSP90 efficiently block necroptosis by preventing RIP3 activation in HT-29. Cells with knocked down CDC37 were unable to respond to necroptosis stimuli (Li D et al. 2015). Further, geldanamycin, an inhibitor of HSP90, and siRNA/shRNA of HSP90α, protected cultured neurons from oxygen-glucose deprivation induced necroptosis by decreasing RIP3 expression (Wang Z et al. 2018). Geldanamycin was reported to nhibit programmed necrosis by suppressing RIPK3 protein expression (Cho YS et al. 2009).Moreover, the HSP90:CDC37 complex was found to interact and regulate the stability of mixed lineage kinase domain-like (MLKL), the downstream effector of the necroptotic signalling pathway (Bigenzahn JW et al. 2016; Jacobsen AV et al. 2016; Zhao XM et al. 2016).