GSK963 is a chiral, highly potent and selective inhibitor of RIP1 kinase, with an IC50 of 29 nM. GSK963 is a selective and potent inhibitor of necroptosis in murine and human cells in vitro[1].
GSK963 is >10 000-fold selective for RIP1 over 339 other kinases, lacks measurable activity against IDO and has an inactive enantiomer, GSK962, which can be used to confirm on-target effects[1].
GSK963 (2 mg/kg) results in a complete protection from TNF+zVAD-induced temperature loss. GSK963 (0.2 mg/kg) also shows a significant response[1].
[1]. Berger SB, et al. Characterization of GSK'963: a structurally distinct, potent and selective inhibitor of RIP1 kinase. Cell Death Discov. 2015 Jul 27;1:15009.