KI-301690 (KI 301690) is a novel potent, specific DDR1 inhibitor, synergized with gemcitabine to suppress the growth of pancreatic cancer cells.
KI-301690 displayed the strongest binding affinity for DDR1 (percent of control [POC] = 9) through a panel of 50 oncogenic kinases at 1 uM.
KI-301690 inhibited p-DDR1 expression in a dose dependent manner in pancreatic cancer cells.
KI-301690 (1-20 uM) decreased proliferative ability in PANC-1 cells in a dose and time-dependent manner.
KI-301690 effectively inhibited expressions of major ECM components by binding collagen, increased gemcitabine sensitivity when used in combination.
KI-301690 effectively blocked DDR1/PYK2/FAK signaling in pancreatic cancer cells combined with gemcitabine.
KI-301690 (30 mg/kg) and gemcitabine (3 mg/kg) for 45 days displays antitumor effects in a pancreatic cancer xenograft model, effectively decreased the expression of p-DDR, p-PYK2, and p-FAK.