CI-988 hemihydrate (PD134308) is a potent and selective orally active CCK2R (cholecystokinin 2 receptor) antagonist, with an IC50 of 1.7 nM for mouse cortical CCK2. It is over 1600 times more selective for CCK2 than for CCK1 receptors. CI-988 hemihydrate exhibits anxiolytic and antitumor properties.

CI-988 demonstrates high affinity (K i of 4.5 nM) in inhibiting specific 125 I-BH-CCK-8 binding to NCI-H727 cells. It significantly blocks ROS increases caused by CCK-8 in these cells. At a concentration of 3 µM, CI-988 inhibits both basal and CCK-8-stimulated growth of NCI-H727 cells. It also prevents CCK-8 from inducing ERK phosphorylation and cytosolic Ca 2+ elevation. CI-988 dose-dependently suppresses CCK-8-induced EGFR transactivation in these cells. At 1 µM and 10 µM, it shows weak to strong inhibition of 0.1µM CCK-8's effect on EGFR tyrosine phosphorylation. Additionally, CI-988 antagonizes CCK-8's ability to cause EGFR or ERK tyrosine phosphorylation associated with lung cancer.

Daily oral administration of CI-988 at a dose of 10 mg/kg over 20 days effectively suppresses the growth of colorectal cancer in a xenograft mouse model.