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| Targets |
The primary target of devazepide is the cholecystokinin A (CCK-A) receptor, also known as the CCK1 receptor. CCK-A receptors are G protein-coupled receptors that are primarily located in the gastrointestinal tract and certain regions of the central nervous system. They mediate the physiological effects of cholecystokinin (CCK), a peptide hormone that is released from the small intestine in response to food intake. CCK-A receptor activation stimulates pancreatic enzyme secretion, gallbladder contraction, and inhibition of gastric emptying, and also contributes to satiety (the feeling of fullness). Devazepide acts as a potent antagonist at the CCK-A receptor, blocking these effects. The compound has high potency at peripheral CCK-A receptors (rat pancreatic: IC₅₀ = 45 pM; bovine gallbladder: IC₅₀ = 81 pM) and lower potency at central CCK receptors (guinea pig brain: IC₅₀ = 245 nM).
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| ln Vitro |
In vitro, devazepide demonstrates potent antagonist activity at the cholecystokinin A receptor. It has IC₅₀ values of 45 pM at the rat pancreatic CCK receptor, 81 pM at the bovine gallbladder CCK receptor, and 245 nM at the guinea pig brain CCK receptor. The compound's activity is typically characterized using radioligand binding assays with membrane preparations from tissues expressing CCK-A receptors and radiolabeled CCK or selective CCK-A antagonists. Functional assays, such as measuring CCK-stimulated amylase secretion from pancreatic acini or CCK-induced gallbladder contraction, can be used to assess the compound's antagonist activity. Devazepide's high potency at peripheral CCK-A receptors makes it a valuable tool for studying the role of CCK in gastrointestinal function and satiety.
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| ln Vivo |
Devazepide (oral gavage; 4 mg/kg; twice daily) causes microlithiasis and gallstone development in mice by dramatically accelerating the growth and crystallization of cholesterol [2]. The effects of devazepide (intraperitoneal injection; 0.1–1 mg/kg) on cerulein- and apomorphine-induced hypokinesia in mice, as well as spontaneous locomotor activity, are opposing [3].
In vivo, devazepide demonstrates potent antagonist activity at CCK-A receptors, blocking the anorectic response to CCK-8 and increasing food intake in rats. The compound is effective following systemic and intracerebroventricular administration. Devazepide's ability to increase food intake has made it a valuable tool for studying the role of CCK in the regulation of appetite and satiety. The compound has also been studied for its potential therapeutic applications in gastrointestinal disorders. Its oral activity makes it suitable for in vivo studies. The compound's effects on food intake and gastrointestinal function have been well-characterized in animal studies. |
| Enzyme Assay |
In vitro receptor binding assays for devazepide measure its affinity for the cholecystokinin A receptor. Radioligand binding studies are performed using membrane preparations from tissues expressing CCK-A receptors (such as rat pancreas, bovine gallbladder, or guinea pig brain) and radiolabeled CCK or selective CCK-A antagonists such as [³H]-devazepide or [¹²⁵I]-CCK-8. Competition binding experiments with varying concentrations of devazepide determine its binding affinity (IC₅₀ or Ki) for the CCK-A receptor in different tissues. These assays are essential for characterizing the compound's potency and selectivity at the CCK-A receptor.
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| Cell Assay |
In vitro cell-based functional assays for devazepide evaluate its antagonist activity at the CCK-A receptor. Cells expressing recombinant CCK-A receptors or tissues expressing native CCK-A receptors (such as pancreatic acini or gallbladder smooth muscle) are treated with varying concentrations of devazepide in the presence or absence of CCK-8. Functional readouts include CCK-stimulated amylase secretion from pancreatic acini, CCK-induced gallbladder contraction, or CCK-stimulated intracellular calcium mobilization. The compound's ability to inhibit these responses confirms its antagonist activity and provides data on its potency.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6J mice [2]
Doses: 4 mg/kg Route of Administration: po (oral gavage); 4 mg/kg; twice (two times) daily Experimental Results:Increased possibility of gallstone formation by impairing gallbladder emptying function . Disrupts biliary cholesterol metabolism and enhances intestinal cholesterol absorption in mice. In vivo animal studies for devazepide have been conducted to evaluate its effects on food intake and gastrointestinal function. In typical studies, rats or other animals are administered devazepide orally or intraperitoneally, and food intake is measured over a defined period. The compound's ability to increase food intake is assessed, and its effects on meal patterns, feeding behavior, and body weight are evaluated. Additionally, the compound's effects on pancreatic secretion, gallbladder contraction, and gastric emptying can be assessed. These studies have demonstrated that devazepide blocks the anorectic effects of CCK and increases food intake. |
| ADME/Pharmacokinetics |
Devazepide has a molecular weight of 408.45 and a chemical formula of C₂₅H₂₀N₄O₂. As a small-molecule CCK-A receptor antagonist, it is orally active. Detailed pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion are established in the pharmacological literature. The compound is well-absorbed after oral administration and distributed to various tissues. It is metabolized in the liver and excreted primarily in bile and urine. Its half-life in rats is approximately 2-3 hours. Devazepide's oral bioavailability and brain penetration make it suitable for studying central and peripheral CCK-A receptor-mediated effects.
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| Toxicity/Toxicokinetics |
Devazepide is generally well-tolerated in animal studies, with the primary effects being related to its mechanism of action as a CCK-A receptor antagonist. The compound can increase food intake and affect gastrointestinal function. Specific toxicity data for devazepide is not extensively reported in the publicly available literature. The compound is classified as a research-grade chemical and is not intended for human use. Standard laboratory safety precautions should be followed when handling devazepide.
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| References |
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| Additional Infomation |
Devazepide is an indole carboxamide formed by the condensation of the carboxyl group of indole-2-carboxylic acid with the outer ring amino group of (3S)-3-amino-1-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepine-2-one. It is a cholecystokinin antagonist used to treat gastrointestinal disorders. It has multiple functions, including as a cholecystokinin antagonist, gastrointestinal drug, antitumor drug, and apoptosis inducer. It is a 1,4-benzodiazepine and indole carboxamide compound. It is a benzodiazepine derivative that acts on the cholecystokinin A (CCKA) receptor, antagonizing the physiological and behavioral effects of CCK-8 (sincallide), such as pancreatic stimulation and appetite inhibition.
Devazepide (CAS# 103420-77-5) is a potent and orally active CCK-A receptor antagonist. It blocks the anorectic response to CCK-8 and increases food intake in rats. The compound has IC₅₀ values of 45 pM at the rat pancreatic CCK receptor and 81 pM at the bovine gallbladder CCK receptor. Devazepide is effective for gastrointestinal disorders and is used as a research tool to study the role of CCK in appetite regulation and gastrointestinal function. It has a molecular weight of 408.45. Devazepide has not received FDA approval for any indication. |
| Molecular Formula |
C25H20N4O2
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|---|---|
| Molecular Weight |
408.45
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| Exact Mass |
408.159
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| CAS # |
103420-77-5
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| PubChem CID |
443375
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.31g/cm3
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| Boiling Point |
758.6ºC at 760mmHg
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| Flash Point |
412.6ºC
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| Vapour Pressure |
6.56E-23mmHg at 25°C
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| Index of Refraction |
1.696
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| LogP |
3.629
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
716
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C2=CC=CC=C2C(=N[C@@H](C1=O)NC(=O)C3=CC4=CC=CC=C4N3)C5=CC=CC=C5
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| InChi Key |
NFHRQQKPEBFUJK-HSZRJFAPSA-N
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| InChi Code |
InChI=1S/C25H20N4O2/c1-29-21-14-8-6-12-18(21)22(16-9-3-2-4-10-16)27-23(25(29)31)28-24(30)20-15-17-11-5-7-13-19(17)26-20/h2-15,23,26H,1H3,(H,28,30)/t23-/m1/s1
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| Chemical Name |
N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-1H-indole-2-carboxamide
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| Synonyms |
L 364,718; Devazepide [INN]; Devazepide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~489.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (12.24 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 5 mg/mL (12.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4483 mL | 12.2414 mL | 24.4828 mL | |
| 5 mM | 0.4897 mL | 2.4483 mL | 4.8966 mL | |
| 10 mM | 0.2448 mL | 1.2241 mL | 2.4483 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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