The ultimate goal of our project is to develop novel therapeutics effective in chronic kidney diseases that normally develop fibrosis, lead to end stage renal disease and require renal replacement therapy. This SBIR phase 2 application builds on the results obtained in phase 1 where novel and selective small molecule antagonists were discovered that prevent the progression of renal fibrosis in a unilateral ureteral obstruction (UUO) animal model. Leads identified in phase 1 will be optimized for drug-like and ADME properties. Candidate compounds meeting the selection criteria will be assessed for safety in vivo and the best compound will be examined in several different animal models of chronic kidney disease to delineate a development path in the clinical setting.