BT1137

BT1137 (also known as D4G) is a preclinical boron-based small molecule inhibitor of the Shroom3-ROCK (Rho-associated coiled-coil containing protein kinase) protein-protein interaction (P2I). Developed by researchers at Yale University and the Icahn School of Medicine at Mount Sinai, BT1137 is designed to target renal tubulointerstitial fibrosis (TIF) in chronic kidney disease (CKD), particularly in patients carrying the high-expressor Shroom3 risk allele (rs17319721). BT1137 binds to the SHROOM-binding domain of ROCK1 and ROCK2, preventing their interaction with the ASD2 domain of Shroom3. This inhibition blocks Shroom3-mediated ROCK activation, reduces MYPT1 phosphorylation, downregulates profibrotic and pro-inflammatory signaling pathways (such as TGF-beta and Wnt/beta-catenin), and attenuates renal fibrosis in vivo.

Other names

D4GD-4GD 4Gpotassium trifluoro(4-(2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazolin-4-yl)phenyl)borate