2-[(3R)-1-(2,2-diethoxyethyl)-3-[(4-methylphenyl)carbamoylamino]-2-oxoindol-3-yl]-N-(4-methylphenyl)acetamide

Uses

AG-041R is a potent and selective CCK2 Receptor/Gastrin antagonist. AG-041R inhibits gastrin-evoked secretion of pancreastatin with an IC50 of 2.2 nM. AG-041R inhibits cell growth of Mastomys ECL carcinoid tumor cells[1][2].

Biological Activity

ag-041r is a cholecystokinin-b/gastrin receptor (gastrin/cck-b) antagonist [1]. the gastrin/cck-b receptor is a regulator of gastric acid secretion and mucosal growth. the gastrin/cck-b is abundantly expressed in mammalian stomach [2].

in vitro

in rabbit primary chondrocytes, ag-041r (0.1 μm) stimulated the cell growth and proliferation, but suppressed with 10 μm. treatment with ag-041r (1 μm) for 28 days accelerated the chondrocyte growth and increased the cell number [1]. in chondrocytes incubated with 0.1 and 1 μm ag-041r, synthesis of gag increased with culture, and amounts accumulated in the composites increased [1]. 10 μm ag-041r might be even toxic to the cells and total rna levels [1]. the ratio of the amounts of two chondroitin sulfate isomers, chondroitin-6-sulfate to chondroitin-4-sulfate, an indicator of cartilage maturation, increased with 1 μm but decreased with 10 μm ag-041r [1].

in vivo

in a preclinical toxicological study on rats, oral administration of high dose of ag-041r stimulated systemic cartilage hyperplasia, including the trachea, the intervertebral disk and the articular cartilage. daily intraarticular injection of ag-041r for 3 weeks into rat knee joints also induced cartilage hyperplasia in marginal regions of the femoral condyle without affecting other tissues [1].

References

[1] ochi m, kawasaki k, kataoka h, et al. ag-041r, a gastrin/cck-b antagonist, stimulates chondrocyte proliferation and metabolism in vitro[j]. biochemical and biophysical research communications, 2001, 283(5): 1118-1123.
[2] langhans n, rindi g, chiu m, et al. abnormal gastric histology and decreased acid production in cholecystokinin-b/gastrin receptor-deficient mice[j]. gastroenterology, 1997, 112(1): 280-286.