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.

Structural 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 as PowerPoint slide