Beneficial effects of a novel inhibitor of platelet-derived growth factor receptor autophosphorylation in the rat with mesangial proliferative glomerulonephritis.

1. Our original compound, Ki6896 ((4-t-butylphenyl)(4-[(6,7-dimethoxy-4-quinolyl) oxy]phenyl) methanone) strongly inhibited the autophosphorylation of platelet-derived growth factor (PDGF) beta-receptor (IC50=0.31 microM) and that of basic fibroblast growth factor receptor (IC50=3.1 microM), whereas it did not inhibit some other kinases. 2. The [3H]thymidine incorporation and the growth of mesangial cells under the stimulation of PDGF were inhibited by Ki6896 in a dose-dependent manner. 3. In the mesangial proliferative glomerulonephritis rats induced by anti-Thy-1 monoclonal antibody, glomerulosclerosis was ameliorated and the number of glomerular proliferating cells was decreased by the daily administration of Ki6896. However, the accumulation of type I collagen and fibronectin in the glomeruli was not suppressed by Ki6896.