BT173 is a novel inhibitor of homeodomain interacting protein kinase 2 (HIPK2 ), attenuating renal fibrosis through suppression of the TGF-ß1/Smad3 pathway.

BT173 strongly inhibited the ability of HIPK2 to potentiate the downstream transcriptional activity of Smad3 in kidney tubular cells. Binding of BT173 to HIPK2 did not inhibit HIPK2 kinase activity but rather, interfered allosterically with the ability of HIPK2 to associate with Smad3. In vitro, treatment with BT173 inhibited TGF-β1–induced Smad3 phosphorylation and Smad3 target gene expression in human renal tubular epithelial cells. [1]

In vivo, administration of BT173 decreased Smad3 phosphorylation and mitigated renal fibrosis and deposition of extracellular matrix in unilateral ureteral obstruction and Tg26 mouse models of renal fibrosis [1].