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 ylphenyl){4-[(6,7-dimethoxy-4-quinoly l)oxy]phenyl} methanone) strongly inhibited the autophosphorylation of platelet-derived growth factor (PDGF) beta-receptor (IC50 = 0.31 mu M ) and that of basic fibroblast growth factor receptor (IC50 = 3.1 mu M ), whereas it did not inhibit some other kinases. 2. The [H-3]thymidin e incorporation and the growth of mesangial cells under the stimulatio n of PDGF were inhibited by Ki6896 in a dose-dependent manner. 3. In t he mesangial proliferative glomerulonephritis rats induced by anti-Thy -1 monoclonal antibody, glomerulosclerosis was ameliorated and the num ber of glomerular proliferating cells was decreased by the daily admin istration of Ki6896. However, the accumulation of type I collagen and fibronectin in the glomeruli was not suppressed by Ki6896. (C) 1998 El sevier Science Inc.