CI-988

CI-988 (PD134308) is a potent, selective and orally active CCK2R (cholecystokinin 2 receptor) antagonist with an IC₅₀ of 1.7 nM for mouse cortex CCK2. CI-988 shows >1600-fold selectivity for CCK2 over CCK1 receptor. CI-988 has anxiolytic and anti-tumor effects^[1][2][3]. IC50 & Target: IC50: 1.7 nM (Mouse cortex CCK2); 2717 nM (Rat pancreas CCK1)^[2] In Vitro: CI-988 inhibits specific ¹²⁵I-BH-CCK-8 binding to NCI-H727 cells with high affinity (K_i of 4.5 nM). The increase in ROS caused by CCK-8 addition to NCI-727 cells is blocked significantly by CI-988. CI-988 (3 µM) inhibits the basal growth of NCI-H727 cells or that stimulated by CCK-8. CI-988 inhibits the ability of CCK-8 to cause ERK phosphorylation and elevate cytosolic Ca^2+[1].
CI-988 inhibits in a dose-dependent manner the ability of CCK-8 to cause EGFR transactivation in NCI-H727 cells. CI-988 at doses of 1 and 10 µM weakly and strongly, respectively, inhibits the ability of 0.1µM CCK-8 to increase EGFR tyrosine phosphorylation. CI-988 antagonizes the ability of CCK-8 to cause lung cancer EGFR or ERK tyrosine phosphorylation^[1]. In Vivo: CI-988 (10 mg/kg; p.o.; daily; for 20 days) inhibits the growth of colorectal cancer in xenografts model mice^[3].