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].

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].

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].

[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.

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.)