2-{[3-cyano-4-(4-methylphenyl)-6-oxo-1,4,5,6-tetrahydropyridin-2-yl]sulfanyl}-N-(1,3-thiazol-2-yl)acetamide

Necrostatin-34 (Nec-34), a RIPK1 kinase inhibitor, stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain[1]. Necrostatin-34 (Nec-34) exhibits IC50 values of 667 nM and 134 nM for TNFα in FADD def-Jurkat cells and L939 cells, respectively[1].Necrostatin-34 (Nec-34, 10 μM) inhibits the dimerization-induced RIPK1 activation as examined by phosphorylation of Ser166 (p-S166) of RIPK1, a biomarker for RIPK1 activation[1].Necrostatin-34 (Nec-34) may block TNFα-induced complex II formation by inhibiting the activation of RIPK1 kinase[1].

[1]. Huyan Meng, et al. Discovery of a cooperative mode of inhibiting RIPK1 kinase. Cell Discov. 2021 Jun 1;7(1):41.