In Vitro: SYN1143 (Compound I) (10-1000 nM; 1 h) inhibits c-Met-mediated signaling and functional activity in HT-29 and BxPC3 cells. SYN1143 (10-1000 nM; 1 h) inhibits RON-mediated signaling and functional activity in NIH3T3 RON and BxPC3 cells. SYN1143 (0.3-30 μM; 2 h or 3 d) inhibits c-Met signaling and cell proliferation in MC3T3-E1 and C3H10T1/2 cells. SYN1143 (0.3-2 μM; 4-12 d) potentiates osteogenic differentiation of precursor cells.
In Vivo: SYN1143 (10-100 mg/kg; p.o. for 22 d) inhibits the growth of c-Met-dependent and constitutively active RON-expressing tumors in mice. SYN1143 (20-50 μg; transferred into calvarial defects) stimulates bone formation in critical-sized defects of mouse calvarial bone.