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Chemical Compound Review:

T-0632 3-[(3S)-1-(2-fluorophenyl)-6- methoxy-2-oxo...

Synonyms: AC1O3SA4, T 0632, 169042-78-8

This record was replaced with 127948.

Taniguchi, H. et al., Taniguchi, H. et al., Taniguchi, H. et al., Tibaduiza, E.C. et al.

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Disease relevance of 3-[(3S)-1-(2-fluorophenyl)-6-methoxy-2-oxo-3-(tetralin-2-carbonylamino)indol-3-yl]propanoic acid

The effect of T-0632 for caerulein-induced pancreatitis was 4-fold more potent than that for gallbladder emptying [1].

High impact information on 3-[(3S)-1-(2-fluorophenyl)-6-methoxy-2-oxo-3-(tetralin-2-carbonylamino)indol-3-yl]propanoic acid

Here, we report that a non-peptide compound, T-0632, binds with micromolar affinity to the human GLP-1R and blocks GLP-1-induced cAMP production [2].
The Ki value of T-0632 for the CCKA receptor was estimated to be 0.24 nM, which was 23 000-fold less than the Ki value (5600 nM) for guinea pig CCKB receptor [3].
In dogs, T-0632 and loxiglumide maximally inhibited CCK-8-stimulated pancreatic amylase secretion at doses of 0.01 and 10 mg/kg, respectively [1].
In rats, intravenously administered T-0632, L-364,718 and loxiglumide dose dependently inhibited cholecystokinin octapeptide (CCK-8)-stimulated pancreatic exocrine secretion with estimated ED50 values of 0.025, 0.016 and 1.8 mg/kg, respectively [1].
In the isolated rabbit gallbladder smooth muscle, T-0632 and loxiglumide competitively inhibited CCK-8-induced contraction with pA2 values of 8.5 and 7.0, respectively [3].

Biological context of 3-[(3S)-1-(2-fluorophenyl)-6-methoxy-2-oxo-3-(tetralin-2-carbonylamino)indol-3-yl]propanoic acid

T-0632, L-364,718 and loxiglumide inhibited CCK-8 (100 pM)-stimulated amylase release from rat pancreatic acini in a concentration-dependent manner with IC50 values of 5.0 nM, 5.0 nM and 3.0 microM, respectively [3].
In mice, orally administered T-0632 prevented caerulein-induced pancreatitis, CCK-8-induced inhibition of gastric emptying and CCK-8-induced gallbladder emptying in dose-dependent manners with ED50 values of 0.028, 0.04, and 0.12 mg/kg, respectively [1].

Anatomical context of 3-[(3S)-1-(2-fluorophenyl)-6-methoxy-2-oxo-3-(tetralin-2-carbonylamino)indol-3-yl]propanoic acid

The inhibitory effects of T-0632 and loxiglumide in gallbladder smooth muscle were readily reversible, but L-364,718 showed a long-lasting inhibition [3].
In rats, orally administered T-0632 potently prevented the caerulein-induced increases in pancreatic digestive enzymes in plasma and suppressed the histological changes in the pancreas [4].
In pancreatic duct ligation (3 hr)-induced pancreatitis, caerulein injection (1 microgram/kg, s.c.) caused a further increase in plasma amylase activity, and T-0632 (0.01, 0.1 mg/kg, p.o.) dose-dependently decreased the aggravation by caerulein [4].

References

Pharmacological profile of T-0632, a novel potent and selective CCKA receptor antagonist, in vivo. Taniguchi, H., Yazaki, N., Yomota, E., Shikano, T., Endo, T., Nagasaki, M. Eur. J. Pharmacol. (1996) [Pubmed]
A small molecule ligand of the glucagon-like peptide 1 receptor targets its amino-terminal hormone binding domain. Tibaduiza, E.C., Chen, C., Beinborn, M. J. Biol. Chem. (2001) [Pubmed]
Pharmacological profile of T-0632, a novel potent and selective CCKA receptor antagonist, in vitro. Taniguchi, H., Yazaki, N., Endo, T., Nagasaki, M. Eur. J. Pharmacol. (1996) [Pubmed]
Effect of T-0632, a cholecystokininA receptor antagonist, on experimental acute pancreatitis. Taniguchi, H., Yomota, E., Kume, E., Shikano, T., Endo, T., Nagasaki, M. Jpn. J. Pharmacol. (1997) [Pubmed]

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