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ID: ALA5143583
Journal: Bioorg Med Chem Lett
Title: Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors.
Authors: Zhang Z, Chen L, Tian H, Liu M, Jiang S, Shen J, Wang K, Cao Z.
Abstract: A deepening understanding of the relationship between transient receptor potential canonical channel 5 (TRPC5) and chronic kidney disease (CKD), has led to the emergence of several types of TRPC5 inhibitors displaying clear therapeutic effect. Herein, we report the synthesis and biological evaluation of a series of pyrroledione TRPC5 inhibitors, culminating in the discovery of compound 16g with subtype selectivity. Compared with GFB-8438, a potent TRPC5 inhibitor (Goldfinch Bio), compound 16g showed improved inhibition of TRPC5 and enhanced protective effect against protamine sulfates (PS)-induced podocyte injury in vitro. In addition, compound 16g did not induce cell death in primary cultured hepatocytes and immortalized podocytes in a preliminary toxicity assessment, indicating its utility as a potent and safe inhibitor for studying the function of TRPC5.
CiteXplore: 35143983