c-Met-IN-22 (compound 51am) is an orally active c-Met inhibitor with an IC50 value of 2.54 nM. It exhibits both antiproliferative and antitumor activities and can induce apoptosis.

c-Met PDGFRβ:513 nM, c-Met Y1235D:54.2 nM, c-Met Fit4:276 nM, c-Met PDGFRα:425 nM, c-Met Y1230H:45.8 nM, c-Met kit:4.94 nM, c-Met (WT):2.54 nM, c-Met VEGFR2:527 nM, c-Met M1250T:26.5 nM, c-Met H1094R:93.6 nM, c-Met Fit3:6.12 nM, c-Met D1228H:29.4 nM, c-Met Ron:3.83 nM

c-Met-IN-22 demonstrates antiproliferative activity in cell lines MNK-45, A-549, HT-29, MDA-MB-231, HUVEC, and FHC, with IC₅₀ values of 0.092, 0.83, 0.68, 3.94, 2.54, and 8.63 μM, respectively. It also inhibits the mutants H1094R, D1228H, Y1230H, Y1235D, and M1250T, with IC₅₀ values of 93.6, 29.4, 45.8, 54.2, and 26.5 nM, respectively. When applied at concentrations of 0, 2.5, 5.0, and 10.0 μM for 24 hours, c-Met-IN-22 inhibits the phosphorylation of c-Met in MKN-45 cells in a dose-dependent manner. Additionally, at concentrations of 0.4, 0.8, and 1.2 μM for 24 hours, it induces cell cycle arrest at the G2 phase and apoptosis in MNK-45 cells, also in a dose-dependent manner.

Administered orally at 10 mg/kg, c-Met-IN-22 demonstrates excellent bioavailability (F=69%) and a half-life of 5.6 hours in BALB/c mice, with a clearance rate of 0.87 L/h•kg. When given intravenously at 1.5 mg/kg, c-Met-IN-22 exhibits a half-life of 3.2 hours in BALB/c mice.