2361988-77-2

cRIPGBM chloride, an orally active, proapoptotic derivative. cRIPGBM can be generated from glioblastoma multiforme (GBM) cancer stem cells (CSCs). cRIPGBM(chloride) targets to receptor-interacting protein kinase 2 (RIPK2) to induce caspase 1-dependent apoptosis. cRIPGBM(chloride) suppresses the formation of RIPK2/TAK1 (prosurvival complex), and increases the formation of RIPK2/caspase 1 (proapoptotic complex). cRIPGBM(chloride) exerts potent anti-tumor activity in vivo in animal models[1].

cRIPGBM is an apoptosis inducer (GBM-1/-5/-39 EC50 = 63/95/290 nM; human neural progenitor cells (NPCs)/astrocytes/lung fibroblasts EC50 = 190/710/960 nM) th at binds receptor-interacting protein kinase 2 (RIPK2RIP2) and promotes the formation of a proapoptotic RIPK2/caspase-1 complex. Cell type-selective metabolic redox conversion of RIPGBM to cRIPGBM in glioblastoma multiforme (GBM) cancer stem cells (CSCs) form the basis of selective GBM CSCs apoptosis induction by RIPGBM over non-GBM cultures.

Caspase-1; RIPK2

[1] Lucki NC, et al. A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancer. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6435-6440. DOI:10.1073/pnas.1816626116