RLA-23174 (Rila Therapeutics)

RLA-23174 (also known as HIPK2i-174 or YL-23174) is a first-in-class, orally bioavailable small molecule allosteric inhibitor of homeodomain-interacting protein kinase 2 (HIPK2). Developed by Rila Therapeutics in collaboration with Shanghai Yingli Pharmaceutical and the Icahn School of Medicine at Mount Sinai, RLA-23174 is designed to treat chronic kidney disease (CKD), renal fibrosis, focal segmental glomerulosclerosis (FSGS), and other fibrotic diseases. Unlike conventional kinase inhibitors, RLA-23174 selectively disrupts the protein-protein interaction between HIPK2 and Smad3, thereby suppressing downstream TGF-β/Smad3 signaling without inhibiting the kinase activity of HIPK2 or affecting p53 pathways. This targeted allosteric mechanism allows the drug to exert potent anti-fibrotic and renoprotective effects while avoiding the systemic toxicities and oncogenic concerns associated with complete HIPK2 or TGF-β blockade. RLA-23174 is currently in Phase I/II clinical development for chronic kidney disease and renal fibrosis.

Other names

Homeodomain interacting protein kinase 2 inhibitor - Rila Therapeutics