SR 27897 is a potent and selective non-peptide antagonist of the cholecystokinin type A (CCK_A) receptor. Its inhibition constant (K_i) for rat pancreatic CCK_A receptors is 0.2 nM [1].
It is highly selective for CCK_A receptors over CCK_B receptors (IC₅₀ ratio of 800) and gastrin receptors (IC₅₀ ratio of approximately 5000) [1].

Lintitript (SR 27897) is a competitive antagonist of cholecystokinin (CCK)-stimulated contraction of the guinea pig gallbladder and amylase release from isolated rat pancreatic acini (pA2 = 7.50) in vitro. (pA2 = 9.57) [1]. When liganditript is applied to the CCK1 receptor site in the rat pancreas (IC50 0.58 nM) and the CCK 2 site in the guinea pig cortex (IC2 479 nM), it inhibits [125I]CCK binding in a concentration-dependent manner. The binding of [125I]gastrin to the gastrin receptor is inhibited by lintitript. Without altering the maximum number of receptors (Bmax = 1800 to 1770 fmol/mg), liganditript (0.5 nM) raises the CCK dissociation constant of CCK A receptors (Kd = 1.8 to 7.2 nM) [1].

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In radioligand binding assays using rat pancreatic membranes (CCK_A receptors), SR 27897 inhibited [¹²⁵I]CCK binding with an IC₅₀ of 0.58 ± 0.07 nM. In guinea pig cortical membranes (CCK_B receptors), it inhibited binding with an IC₅₀ of 479 ± 79 nM. In isolated guinea pig gastric glands (gastrin receptors), it inhibited [¹²⁵I]gastrin binding with an IC₅₀ of 2883 ± 1012 nM [1].
Scatchard analysis of [¹²⁵I]CCK binding to rat pancreatic membranes in the presence of 0.5 nM SR 27897 showed an increase in the dissociation constant (K_d) from 1.8 nM to 7.2 nM, with no change in the maximum number of binding sites (B_max), indicating a competitive interaction at the CCK_A receptor [1].
In isolated rat pancreatic acini, SR 27897 (100-3000 nM) caused a parallel rightward shift of the concentration-response curve for CCK-stimulated amylase release without reducing the maximal response. The Schild plot was linear with a slope not significantly different from unity (1.39 ± 0.13), and the calculated pA₂ value was 7.50 ± 0.17. At concentrations up to 10 μM, SR 27897 alone did not stimulate amylase release, indicating it is not a partial agonist [1].
In isolated guinea pig gall bladder strips, SR 27897 (10⁻⁹ - 3x10⁻⁸ M) competitively antagonized CCK-induced contractions, causing a rightward shift of the concentration-response curve. The pA₂ value was 9.51 ± 0.12. It had no intrinsic contractile activity on its own at concentrations up to 10 μM [1].

The action of lintitript (SR 27897; 1 mg/kg, i.v.) totally counteracts the amylase production generated by CCK. Additionally, lintitript prevents mice's gallbladder and stomach from emptying when CCK is present (ED50 = 3 and 72 μg/kg, respectively). When endogenous CCK release is induced by egg yolk in gallbladder emptying regimens, lintitript exhibits high activity (ED50 = 27 μg/kg po) [1].

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In anesthetized rats, intravenous administration of SR 27897 dose-dependently inhibited pancreatic amylase secretion stimulated by CCK (0.25 μg/kg i.v.). A dose of 1.0 mg/kg i.v. of SR 27897 produced a similar level of inhibition as 0.1 mg/kg i.v. of the reference compound L-364,718 [1].
In a mouse model of CCK-induced inhibition of gastric emptying (charcoal meal), SR 27897 administered orally (1 h before CCK) antagonized this effect with an ED₅₀ of 5 μg/kg (95% confidence limits 3–10). When administered intravenously (5 min before CCK), the ED₅₀ was 10 μg/kg (7–16). At an oral dose of 50 μg/kg, the antagonistic effect of SR 27897 lasted for at least 5 hours [1].
In a mouse model of CCK-induced gall bladder emptying (10 μg/kg s.c.), oral administration of SR 27897 1 hour prior to CCK dose-dependently reversed the response with an ED₅₀ of 72 μg/kg (58–86) [1].
In a mouse model using oral egg yolk to stimulate endogenous CCK release, SR 27897 administered orally inhibited gall bladder emptying with an ED₅₀ of 27 μg/kg (13–40). The antagonistic effect of 0.05 mg/kg SR 27897 was sustained for up to 5 hours [1].
When administered alone to fasting mice (without CCK or egg yolk stimulation), oral SR 27897 increased gall bladder weight (indicating relaxation/increased volume). This effect was dose-dependent and statistically significant at doses of 1.0, 3.0, and 5.0 mg/kg. Compared to L-364,718, SR 27897 was approximately 10 times less potent in this effect. In a time-course study, a 100 μg/kg oral dose of SR 27897 significantly increased gall bladder weight for up to 3 hours [1].

Amylase Secretion Assay in Pancreatic Acini: Isolated rat pancreatic acini were prepared by collagenase digestion. Aliquots of the acinar suspension were incubated with various concentrations of CCK in the absence or presence of fixed concentrations of SR 27897 (100, 300, 1000, 3000 nM) for 30 minutes at 37°C. The reaction was terminated by centrifugation, and the supernatant was assayed for amylase activity using the Phadebas reagent. Amylase secretion was expressed as a percentage of the maximal CCK-stimulated release after subtracting basal release [1].
Gall Bladder Contraction Assay: Guinea pig gall bladder strips were suspended in organ baths containing oxygenated Krebs-Henseleit solution at 32°C under a resting tension of 0.5 g. After equilibration, cumulative concentration-response curves for CCK were constructed in the absence or presence of a fixed concentration of SR 27897 (10⁻⁹, 3x10⁻⁹, 10⁻⁸, or 3x10⁻⁸ M), which was added 60 minutes before the agonist. Isometric contractions were recorded, and responses were expressed as a percentage of the maximal control response to CCK [1].

Pancreatic Secretion in Rats:** Fasted rats were anesthetized with sodium pentobarbital. A jugular vein was cannulated for drug administration, and a duodenal cannula was inserted through the duodenal papilla into the pancreaticobiliary duct to collect pancreatic secretion. After a 30-minute equilibration period, basal secretion was collected for two 10-minute periods. SR 27897 (0.10, 0.25, 0.50, 1.00 mg/kg) was administered intravenously 10 minutes before CCK (0.25 μg/kg i.v.) was injected. Secretions were collected for 90 minutes, and amylase concentrations were determined using the Phadebas test. Results were expressed as total milligrams of amylase accumulated over 90 minutes [1].
* **Gastric Emptying Inhibition in Mice:** Fasted mice (10 or 20 per group) were treated with SR 27897 orally (at various times before CCK) or intravenously (5 min before CCK). CCK (100 μg/kg) was administered subcutaneously 5 minutes before an oral charcoal meal (0.3 ml of a suspension containing 10% charcoal, 5% gum arabic, and 1% CM-cellulose). Mice were killed 5 minutes after the charcoal meal. Gastric emptying was defined as the presence of charcoal in the intestine beyond the pyloric sphincter. The number of protected mice per group was noted, and the ED₅₀ was calculated [1].
* **Gall Bladder Emptying in Mice (Exogenous CCK):** Fasted mice (10 or 20 per group) were administered SR 27897 orally at various doses. One hour later, CCK (10 μg/kg) was injected subcutaneously. Mice were killed by cervical dislocation 15 minutes after CCK injection. The gall bladder was removed and weighed. The ED₅₀ for inhibiting CCK-induced gall bladder emptying was calculated [1].
* **Gall Bladder Emptying in Mice (Endogenous CCK):** Fasted mice were administered SR 27897 orally at various doses. One hour later, they received an oral administration of egg yolk (0.5 ml of a 30% suspension in 0.9% NaCl) to stimulate endogenous CCK release. Mice were killed 15 minutes later, and their gall bladders were removed and weighed. The ED₅₀ for inhibiting egg yolk-induced gall bladder emptying was calculated [1].
* **Effect on Gall Bladder Weight in Fasting Mice:** Fasted mice were treated orally with SR 27897 at various doses. They were killed 1 hour later (for dose-effect studies) or at various time points after a fixed dose (for time-course studies). Their gall bladders were removed and weighed. Results were expressed as mg gall bladder weight per kg body weight [1].

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Pancreatic Secretion in Rats: Fasted rats were anesthetized with sodium pentobarbital. A jugular vein was cannulated for drug administration, and a duodenal cannula was inserted through the duodenal papilla into the pancreaticobiliary duct to collect pancreatic secretion. After a 30-minute equilibration period, basal secretion was collected for two 10-minute periods. SR 27897 (0.10, 0.25, 0.50, 1.00 mg/kg) was administered intravenously 10 minutes before CCK (0.25 μg/kg i.v.) was injected. Secretions were collected for 90 minutes, and amylase concentrations were determined using the Phadebas test. Results were expressed as total milligrams of amylase accumulated over 90 minutes [1].
Gastric Emptying Inhibition in Mice: Fasted mice (10 or 20 per group) were treated with SR 27897 orally (at various times before CCK) or intravenously (5 min before CCK). CCK (100 μg/kg) was administered subcutaneously 5 minutes before an oral charcoal meal (0.3 ml of a suspension containing 10% charcoal, 5% gum arabic, and 1% CM-cellulose). Mice were killed 5 minutes after the charcoal meal. Gastric emptying was defined as the presence of charcoal in the intestine beyond the pyloric sphincter. The number of protected mice per group was noted, and the ED₅₀ was calculated [1].
Gall Bladder Emptying in Mice (Exogenous CCK): Fasted mice (10 or 20 per group) were administered SR 27897 orally at various doses. One hour later, CCK (10 μg/kg) was injected subcutaneously. Mice were killed by cervical dislocation 15 minutes after CCK injection. The gall bladder was removed and weighed. The ED₅₀ for inhibiting CCK-induced gall bladder emptying was calculated [1].
Gall Bladder Emptying in Mice (Endogenous CCK): Fasted mice were administered SR 27897 orally at various doses. One hour later, they received an oral administration of egg yolk (0.5 ml of a 30% suspension in 0.9% NaCl) to stimulate endogenous CCK release. Mice were killed 15 minutes later, and their gall bladders were removed and weighed. The ED₅₀ for inhibiting egg yolk-induced gall bladder emptying was calculated [1].
Effect on Gall Bladder Weight in Fasting Mice: Fasted mice were treated orally with SR 27897 at various doses. They were killed 1 hour later (for dose-effect studies) or at various time points after a fixed dose (for time-course studies). Their gall bladders were removed and weighed. Results were expressed as mg gall bladder weight per kg body weight [1].

SR 27897 demonstrated equivalent potency and a long-lasting action after both oral and intravenous administration in various in vivo models, suggesting good oral bioavailability [1].
In the mouse gastric emptying model, the oral and intravenous ED₅₀ values for SR 27897 were not statistically different, indicating comparable efficacy by both routes [1].
The antagonistic effect of orally administered SR 27897 was long-lasting, with significant activity observed for up to 5 hours post-administration in gastric emptying, gall bladder emptying, and gall bladder tone models [1].

[1]. Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors. Eur J Pharmacol. 1993 Feb 23;232(1):13-9.

[2]. Contrasting roles of leu(356) in the human CCK(1) receptor for antagonist SR 27897 and agonist SR 146131 binding. Eur J Pharmacol. 1999 Nov 3;383(3):339-46.

[3]. Regulation of leptin distribution between plasma and cerebrospinal fluid by cholecystokinin receptors. Br J Pharmacol. 2003 Oct;140(4):647-52.

2-[2-[[[4-(2-chlorophenyl)-2-thiazolyl]amino]-oxymethyl]-1-indole]acetic acid is an indole carboxylic acid. Lintitript is a novel, highly specific, and potent CCK-A receptor antagonist. Indications: For the treatment of pancreatic cancer and appetite disorders. Mechanism of Action: Cholecystokinin (CCK) regulates feeding and dopamine-induced behavior in the central and peripheral nervous systems. Lintitript antagonizes the effects of CCK by binding to the CCK-A receptor. This may alter eating habits, but its exact mechanism of action is unclear. Pharmacodynamics: Lintitript SR 27897 is a selective CCK-A receptor antagonist. In February 2000, Sanofi announced that it would stop developing the drug for the treatment of appetite disorders; in September 2002, Sanofi announced that it had completely stopped research on the drug.

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Background: SR 27897 is a new non-peptide antagonist of CCK_A receptors, discovered through optimization of a lead compound from a chemical library screen. It is chemically distinct from other known CCK_A antagonists like the benzodiazepine L-364,718 (devazepide) and glutamic acid derivatives like loxiglumide [1].
Selectivity: A key feature of SR 27897 is its high selectivity for the CCK_A receptor. It is approximately 800-fold more selective for CCK_A over CCK_B receptors and about 5000-fold more selective over gastrin receptors. This selectivity is greater than that of L-364,718, particularly against the gastrin receptor [1].
Efficacy: SR 27897 is a full antagonist with no partial agonist activity in the tested models. It potently and competitively antagonizes CCK's effects in vitro (amylase release, gall bladder contraction) and in vivo (pancreatic secretion, gastric emptying, gall bladder emptying). Its potency varies depending on the tissue and whether CCK is exogenous or endogenous [1].
Potential Applications: Based on its pharmacological profile, SR 27897 was proposed as a useful tool for studying the physiological and pathological roles of CCK in humans, particularly in gastrointestinal functions [1].

C20H14CLN3O3S

411.86

411.044

136381-85-6

122077

White to off-white solid powder

1.49g/cm3

1.723

4.828

2

5

5

28

595

0

ILNRQFBVVQUOLP-UHFFFAOYSA-N

InChI=1S/C20H14ClN3O3S/c21-14-7-3-2-6-13(14)15-11-28-20(22-15)23-19(27)17-9-12-5-1-4-8-16(12)24(17)10-18(25)26/h1-9,11H,10H2,(H,25,26)(H,22,23,27)

2-[2-[[4-(2-chlorophenyl)-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]acetic acid

SR-27897 SR 27897 SR27897

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~242.80 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)