Structure–activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5

Necrostatin-5 (Nec-5) is a novel potent small-molecule inhibitor of necroptosis structurally distinct from previously described Necrostatin-1 (Nec-1), and therefore, represents a new direction for the inhibition of this cellular caspase-independent necrotic cell death mechanism. Here, we describe a series of structural modifications of Nec-5 and the structure–activity relationship (SAR) of Nec-5 series in inhibiting necroptosis.

Graphical abstractStructural effect of substituents on Nec-5, a new class of small molecule inhibitors of necroptosis, was described. Significant influence was found in structural variation of R, R1, R2, and Xn in the parent molecule.Figure optionsDownload full-size imageDownload as PowerPoint slide