Pharmacological properties of ureido-acetamides, new potent and selective non-peptide CCKB/gastrin receptor antagonists

Bertrand, Philìppe; Böhme, Georg Andrees; Durieux, Christiane; Guyon, Claude; Capet, Marc; Jeantaud, Bernadette; Boudeau, Philippe; Ducos, Bertrand; Pendley, Charles; Martin, Gregory E.; Floch, Anne; Doble, Adam

doi:10.1016/0014-2999(94)90737-4

Cited by 32 publications

(10 citation statements)

References 58 publications

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“…The following synthetic ligands of the CCK2R were used ( Fig. 1): L365,260 (Lotti and Chang, 1989), YM022 (Satoh et al, 1995), PD135,158 (Hughes et al, 1990), CR2945 (Revel et al, 1998), RPR101,048 (Bertrand et al, 1994), and GV150,013X (Ursini et al, 2000) were supplied by Merck (Whitehouse Station, NJ), Yamanouchi Pharmaceutical (Tokyo, Japan), Pfizer (Cambridge, UK), Rotta Research Laborotorium (Monza, Italy), SANOFI Aventis (Paris, France), GlaxoSmithKline (Verona, Italy), respectively.…”

Section: Methodsmentioning

confidence: 99%

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Foucaud¹,

Tikhonova²,

Langer³

et al. 2005

Mol Pharmacol

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Cholecystokinin receptor-2 (CCK2R) is a G protein receptor that regulates a number of physiological functions. Activation of CCK2R and/or expression of a constitutively active CCK2R variant may contribute to human diseases, including digestive cancers. Search for antagonists of the CCK2R has been an important challenge during the last few years, leading to discovery of a set of chemically distinct compounds. However, several early-discovered antagonists turned out to be partial agonists. In this context, we carried out pharmacological characterization of six CCK2R antagonists using COS-7 cells expressing the human CCK2R or a CCK2R mutant having a robust constitutive activity on inositol phosphates production, and we investigated the molecular mechanisms which, at a CCK2R binding site, account for these features. Results indicated that three compounds, 3R(ϩ)-N-(

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Section: Methodsmentioning

confidence: 99%

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Foucaud¹,

Tikhonova²,

Langer³

et al. 2005

Mol Pharmacol

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“…CI‐988 (formerly PD 134308) (26) and LY 262691 (27) are compounds more recently available for researchers. Another novel family of CCK‐2 receptor antagonists includes RP 69 758, RP 71 483 and RP 72 540, which are potent and selective but show very low penetration into the brain (28).…”

Section: Introductionmentioning

confidence: 99%

Cholecystokinin and panic disorder

Bourin¹,

Dailly²

2004

Acta Neuropsychiatr.

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“…We selected compounds from the large number of CCK B /gastrin receptor ligands that have been described including L‐365,260 ( Lotti & Chang, 1989 ), PD134,308 ( Hughes et al ., 1990 ), L‐156,586 ( Lam et al ., 1990 ), PD136,450 ( Horwell et al ., 1991 ), PD140,376 ( Hunter et al ., 1993 ), LY262691 ( Howbert et al ., 1993 ), YM022 ( Nishida et al ., 1994 ), L‐740,093 ( Patel et al ., 1994 ), CP‐212,454 ( Lowe et al ., 1994 ), RP72540 ( Bertrand et al ., 1994 ), RP73870 ( Bohme et al ., 1994 ; Pendley et al ., 1995 ), RPR101367 ( Bertrand et al ., 1995 ), GV150013 ( Corsi et al ., 1995 ) and JB93182 ( Kalindjian et al ., 1996 ). When these compounds were originally described there was no mention of data complexity and no suggestion of CCK B /gastrin receptor heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the behaviour of selected CCK_B/gastrin receptor antagonists in radioligand binding assays performed in mouse and rat cerebral cortex

Harper¹,

Griffin²,

Shankley³

et al. 1999

British J Pharmacology

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James Black Foundation, 68 Half Moon Lane, Dulwich, London SE24 9JE, England 1 The previously described complex behaviour of the CCK B /gastrin receptor antagonist, L-365,260, in radioligand binding assays could be explained by a variable population of two binding sites. We have investigated whether other CCK B /gastrin receptor ligands (PD134,308, PD140,376, YM022 and JB93182) can distinguish between these sites. 2 In the mouse cortex assay, Hill slopes were not dierent from unity and the ligand pK I values did not dier when either [ I]-BH-CCK-8S or [3 H]-PD140,376 was used as label as expected for a single site (G 2 ). 3 In the rat cortex, where previous analysis of replicate (n=48) L-365,260 data indicated the presence of two CCK B /gastrin sites (G 1 and G 2 ), the competition data for PD134,308, PD140,376, YM022 and JB93182 could be explained by a homogeneous population of CCK B /gastrin sites because the Hill slope estimates were not signi®cantly dierent from unity. However, the estimated anity values for JB93182 and YM022 were signi®cantly higher and that for PD134,308 was signi®cantly lower than those obtained in the mouse cortex when the same radioligand was used. In view of our previous data obtained with L-365,260, the rat cortex data were also interpreted using a two-site model. In this analysis, SR27897 expressed *9 fold, PD134,308 *13 fold and PD140,376 *11 fold selectivity for the G 2 site. In contrast, JB93182 expressed *23 fold and YM022 *4 fold selectivity for the G 1 site. If the two-site interpretation of the data is valid then, because of its reverse selectivity to L-365,260, JB93182 has been identi®ed as a compound which if radiolabelled could provide a test of this receptor subdivision.

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Pharmacological properties of ureido-acetamides, new potent and selective non-peptide CCKB/gastrin receptor antagonists

Cited by 32 publications

References 58 publications

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Cholecystokinin and panic disorder

Analysis of the behaviour of selected CCK_B/gastrin receptor antagonists in radioligand binding assays performed in mouse and rat cerebral cortex

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Pharmacological properties of ureido-acetamides, new potent and selective non-peptide CCKB/gastrin receptor antagonists

Cited by 32 publications

References 58 publications

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Partial Agonism, Neutral Antagonism, and Inverse Agonism at the Human Wild-Type and Constitutively Active Cholecystokinin-2 Receptors

Cholecystokinin and panic disorder

Analysis of the behaviour of selected CCKB/gastrin receptor antagonists in radioligand binding assays performed in mouse and rat cerebral cortex

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Product

Resources

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Analysis of the behaviour of selected CCK_B/gastrin receptor antagonists in radioligand binding assays performed in mouse and rat cerebral cortex