Cholecystokinin Receptor Antagonist

LY 202769 (Example 26) is a cholecystokinin (CCK) and gastrin receptor (gastrin receptor) antagonist. LY 202769 is applicable for the research of gastrointestinal diseases and central nervous system diseases.

N-Cbz-DL-tryptophan (Z-DL-Trp-OH) is the enantiomer of Tryptophan (HY-N0623) derivative. N-Cbz-DL-tryptophan is a cholecystokinin receptor antagonist.

Devazepide (L-364,718) is a potent, competitive, selective and orally active nonpeptide antagonist of cholecystokinin (CCK) receptor, with IC₅₀s of 81 pM, 45 pM and 245 nM for rat pancreatic, bovine gallbladder and guinea pig brain CCK receptors, respectively. Devazepide (L-364,718) is effective for gastrointestinal disorders.

L-365260 is an orally active and selective antagonist of non-peptide gastrin and brain cholecystokinin receptor (CCK-B), with K_is of 1.9 nM and 2.0 nM, respectively. L-365260 interacts in a stereoselective and competitive manner with guinea pig stomach gastrin and brain CCK receptors. L-365260 can enhance Morphine analgesia and prevents Morphine tolerance.

Sograzepide (Netazepide; YF 476; YM-220) is an extremely potent, highly selective and orally active Gastrin/CCK-B antagonist with an IC₅₀ value of 0.1 nM, has inhibitory effect on Gastrin/CCK-A activity with an IC₅₀ of 502 nM. Sograzepide (Netazepide; YF 476; YM-220) replaces the specific binding of [125I]CCK-8 to the rat brain, cloned canine and cloned human Gastrin/CCK-B receptors, with K_i values of 0.068, 0.62 and 0.19 nM, respectively.

Lorglumide sodium salt (CR-1409 sodium salt) is a potent cholecystokinin (CCK) receptor antagonist.

Proglumide is a nonpeptide and orally active cholecystokinin (CCK)-A/B receptors antagonist. Proglumide selective blocks CCK’s effects in the central nervous system (CNS). Proglumide has ability to inhibit gastric secretion and to protect the gastroduodenal mucosa. Proglumide also has antiepileptic and antioxidant activities.

Dexloxiglumide is an orally active and selective cholecystokinin type A (CCKA) receptor antagonist. Dexloxiglumide is the active enantiomer of Loxiglumide, inhibits smooth muscle cell contractions induced by cholecystokinin-octapeptide (CCK-8). Dexloxiglumide exhibits moderate Caco-2 permeability that is polarized, concentration dependent, and pH dependent. Dexloxiglumide increases MRP1-substrate fluorescein uptake. Dexloxiglumide can be studied in research for gastrointestinal diseases and tumors.

Proglumide sodium is a nonpeptide and orally active cholecystokinin (CCK)-A/B receptors antagonist. Proglumide sodium selective blocks CCK’s effects in the central nervous system (CNS). Proglumide sodium has ability to inhibit gastric secretion and to protect the gastroduodenal mucosa. Proglumide sodium also has antiepileptic and antioxidant activities.

Lintitript (SR 27897) is a highly potent, selective, orally active, competitive and non-peptide cholecystokinin (CCK1) receptor antagonist with an EC₅₀ of 6 nM and a K_i of 0.2 nM. Lintitript displays > 33-fold selectivity more selective for CCK1 than CCK2 receptors (EC₅₀ value of 200 nM). Lintitript increases plasma concentration of leptin and food intake as well as plasma concentration of insulin.

Nastorazepide (Z-360) is an orally active 1,5-benzodiazepine derivative and gastrin/CCK-2 receptor antagonist. Nastorazepide inhibits the specific binding of [³H]CCK-8 to the human CCK-2 receptor with a K_i value of 0.47 nM. Nastorazepide inhibits IL-1β, ephrin B1, VEGF, and HIF-1alpha, reduces Akt and NR2B phosphorylation. Nastorazepide has antitumor activity against pancreatic cancer. Nastorazepide inhibits colorectal cancer liver metastasis and relieves pain.

Loxiglumide is a cholecystokinin (CCK-1) receptor antagonist.

T-0632 is a CCK A receptor antagonist that exhibits significant pharmacological properties in in vitro studies. T-0632 competitively inhibits the binding of [125I]CCK-8 to rat pancreatic CCK A receptors with a K_i value of 0.24 nM, which is significantly lower than the K_i value for guinea pig CCK B receptors. T-0632 has higher selectivity in inhibiting CCK-8-stimulated pancreatic enzyme release, with an IC_50 value of 5.0 nM, which is more advantageous than L-364,718 and loxiglumide. In rabbit gallbladder smooth muscle, the antagonistic effects of T-0632 and loxiglumide are reversible, while L-364,718 shows a persistent inhibitory effect. These results indicate that T-0632 is a highly potent, reversible and more selective CCK A receptor antagonist.

Pranazepide (FR120480) is a selective cholecystokinin-1 receptor (CCK1-R) antagonist with an IC₅₀ of 0.67 nM against CCK1-R. Pranazepide is applicable for the research of pancreatic diseases.

JNJ-26070109 is a high-affinity, competitive, orally bioactive, and selective cholecystokinin 2 (CCK2) receptor antagonist with good pharmacokinetic properties, with pK_is of 8.49, 7.99, and 7.70 for human, rat, and dog CCK2 receptors, respectively. The dual function of CCK2 receptors in regulating gastric acid secretion and growth of the gastrointestinal mucosa make this an attractive and novel target for the research of gastroesophageal reflux disease.

LY 225910 is a selective antagonist for cholecystokinin receptor (CCK2 receptor), which affects the excitatory response to morphine, and leads to morphine sensitization.

PNB-001 is an orally active CCK2 selective ligand and antagonist. PNB-001 has anti-inflammatory and analgesic activities.

L-365260 hemihydrate is an orally active and selective antagonist of non-peptide gastrin and brain cholecystokinin receptor (CCK-B), with K_is of 1.9 nM and 2.0 nM, respectively. L-365260 hemihydrate interacts in a stereoselective and competitive manner with guinea pig stomach gastrin and brain CCK receptors.

A-65186 is a CCK-A receptor antagonist with the activity of inhibiting CCK8-induced amylase secretion. A-65186 has high binding affinity for pancreatic CCK-A receptors, is more than 500 times more selective for CCK-A receptors than for CCK-B receptors, and can inhibit CCK8-induced amylase secretion.

(Rac)-Sograzepide is an antagonist of cholecystokinin B (CCK-B) receptor, and has the potential of reducing the secretion of gastric acid.