Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model.

ABSTRACT: The nonselective Ca²⁺-permeable transient receptor potential (TRP) channels play important roles in diverse cellular processes, including actin remodeling and cell migration. TRP channel subfamily C, member 5 (TRPC5) helps regulate a tight balance of cytoskeletal dynamics in podocytes and is suggested to be involved in the pathogenesis of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS). As such, protection of podocytes by inhibition of TRPC5 mediated Ca²⁺ signaling may provide a novel therapeutic approach for the treatment of proteinuric kidney diseases. Herein, we describe the identification of a novel TRPC5 inhibitor, GFB-8438, by systematic optimization of a high-throughput screening hit, pyridazinone 1. GFB-8438

SUBMITTER: Yu M 

PROVIDER: S-EPMC6862342 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature