RIP1 kinase inhibitor 1 (compound 22) is a highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor (pKi=9.04)[1]. pKi: 9.04 (RIP1 kinase)[1]
RIP1 kinase inhibitor 1 (compound 22) strongly suppresses necroptotic cell death and phosphorylation of MLKL(pMLKL) in human colorectal adenocarcinoma HT-29 cells (nectoptosis, IC50=2 nM; pMLKL, IC50=1.3 nM) as well as mouse L-cells NCTC 929 (nectoptosis, IC50=15 nM; pMLKL, IC50=2.7 nM)[1].
[1]. Yoshikawa M, et al. Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, OrallyAvailable, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships. J Med Chem. 2018 Mar 22;61(6):2384-2409.