GW-788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor. GW-788388 exhibits anti-fibrotic and cardioprotective activities. GW-788388 increases survival in studies of Trypanosoma infection and prevents Chagas disease-induced development of cardiac fibrosis. This compound also attenuates systolic dysfunction and left ventricular remodeling in animal models of myocardial infarction. In animal models of diabetes, GW-788388 decreases the occurrence of renal fibrosis. GW-788388 can inhibit TGF-b and activin signalling in vitro and attenuate renal fibrosis in vivo. By blocking the action of the ALK5 and TbRII kinase receptors, TGF-b-induced growth arrest, EMT, and ECM deposition were inhibited in vitro. TGF-b receptor kinase inhibition should attenuate fibrogenesis and improve the fibrotic outcome for patients suffering from diabetic nephropathy.