| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Cholecystokinin type A receptor (CCKA). CCKA receptors are located primarily in the gastrointestinal system where they regulate gastric emptying, intestinal motility, and sensitivity to distension.
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| ln Vitro |
In vitro, dexloxiglumide inhibits smooth muscle cell contractions induced by cholecystokinin-octapeptide (CCK-8). It exhibits moderate, polarized, concentration-dependent, and pH-dependent Caco-2 cell permeability, and enhances the uptake of MRP1 substrate fluorescein. The compound demonstrates potent antagonist activity at CCKA receptors with higher potency than loxiglumide.
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| ln Vivo |
As an orally active CCKA receptor antagonist, dexloxiglumide modulates gastrointestinal motility and sensitivity. In vivo studies have focused on its effects in animal models of IBS and GERD, where it increases gastric emptying and intestinal motility while modulating visceral sensitivity. However, Phase III clinical trials in women with constipation-predominant IBS did not demonstrate statistically significant superiority over placebo.
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| Enzyme Assay |
CCKA receptor binding assays are typically performed using radioligand binding techniques with membrane preparations from tissues or cells expressing the CCKA receptor. Radiolabeled CCK-8 or selective CCKA antagonists are used as tracers, and competition binding experiments with varying concentrations of dexloxiglumide are conducted to determine binding affinity (Ki). Non-specific binding is determined in the presence of excess unlabeled ligand.
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| Cell Assay |
Functional cell-based assays evaluate the antagonist activity of dexloxiglumide at CCKA receptors. Cells expressing recombinant CCKA receptors are loaded with calcium-sensitive fluorescent dyes, stimulated with CCK-8 to induce intracellular calcium mobilization, and the inhibition of this response by dexloxiglumide is measured. Alternatively, smooth muscle cell contraction assays are used where CCK-8-induced contractions are measured in the presence of the compound.
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| Animal Protocol |
In vivo animal studies for dexloxiglumide typically use rodent models of gastrointestinal motility and visceral hypersensitivity. Compound is administered orally, and endpoints include gastric emptying rate, intestinal transit time, and visceromotor responses to colorectal distension. These models were used to support the compound's advancement into clinical trials for IBS and GERD.
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Following a single oral administration, this product is rapidly and extensively absorbed in the human body, with an absolute bioavailability of 48%. Incomplete bioavailability is due to incomplete absorption and the first-pass effect in the liver. Metabolism/Metabolites Cytochrome P450 (CYP) 3A4/5 and CYP2C9 participate in the metabolism of dexloxigramiylate to O-desmethyldexloxigramiylate. This metabolite is further oxidized to dexloxigramiic acid. These two major metabolites have been identified (accounting for 50% of dexloxigramiylate elimination). However, in human plasma, the parent drug is the major component of the metabolic profile (up to 91%). The parent drug is considered the main contributor to the efficacy of this compound because its major metabolites are not pharmacologically active. The known human metabolites of deloxigramid include 4-[(3,4-dichlorobenzoyl)amino]-5-[3-hydroxypropyl(pentyl)amino]-5-oxovalerate. Dexloxiglumide is orally active with a molecular weight of 461.4 g/mol. It demonstrates moderate Caco-2 cell permeability that is concentration-dependent and pH-dependent, suggesting variable oral absorption. The compound is the D-isomer of loxiglumide and retains all pharmacological properties with enhanced potency. Detailed pharmacokinetic parameters such as half-life, bioavailability, and protein binding are not extensively reported in public literature. |
| Toxicity/Toxicokinetics |
Protein Binding
94-98% Specific toxicity data for dexloxiglumide is not extensively reported in public literature. As a CCKA receptor antagonist that reached Phase III clinical trials, it would have undergone standard preclinical toxicology evaluation. The compound is classified as a research-grade chemical and is not intended for human use outside of clinical trial settings. |
| References |
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| Additional Infomation |
Dexloxiglumide is a glutamate derivative. Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist, currently undergoing Phase III clinical trials only in Europe by Rottapharm, as its trials in the United States have been terminated. As the D-isomer of loxigrammet, it retains all the pharmacological properties of loxigrammet but is more potent. Indications: For the treatment of irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Mechanism of Action: CCKA antagonists target receptors in the gastrointestinal system to promote gastric emptying and intestinal motility, and modulate intestinal sensitivity to distension.
Dexloxiglumide is a selective CCKA receptor antagonist that reached Phase III clinical development for IBS and GERD. It is the active D-enantiomer of loxiglumide with enhanced potency. U.S. development was discontinued in 2003 after Phase III studies in women with constipation-predominant IBS failed to show statistically significant efficacy over placebo. European trials continued with different designs. The compound has not received FDA approval. |
| Molecular Formula |
C21H30N2O5CL2
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|---|---|
| Molecular Weight |
461.3793
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| Exact Mass |
460.153
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| CAS # |
119817-90-2
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| PubChem CID |
65937
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| Appearance |
White to off-white solid powder
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| Density |
1.233g/cm3
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| Boiling Point |
632.2ºC at 760mmHg
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| Flash Point |
336.1ºC
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| Vapour Pressure |
7.51E-17mmHg at 25°C
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| Index of Refraction |
1.537
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| LogP |
4.402
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
30
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| Complexity |
550
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCCCCN(CCCOC)C(=O)[C@@H](CCC(=O)O)NC(=O)C1=CC(=C(C=C1)Cl)Cl
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| InChi Key |
QNQZBKQEIFTHFZ-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C21H30Cl2N2O5/c1-3-4-5-11-25(12-6-13-30-2)21(29)18(9-10-19(26)27)24-20(28)15-7-8-16(22)17(23)14-15/h7-8,14,18H,3-6,9-13H2,1-2H3,(H,24,28)(H,26,27)/t18-/m1/s1
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| Chemical Name |
(4R)-4-[(3,4-dichlorobenzoyl)amino]-5-[3-methoxypropyl(pentyl)amino]-5-oxopentanoic acid
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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 |
| 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 : ~50 mg/mL (~108.37 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.42 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.42 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1674 mL | 10.8371 mL | 21.6741 mL | |
| 5 mM | 0.4335 mL | 2.1674 mL | 4.3348 mL | |
| 10 mM | 0.2167 mL | 1.0837 mL | 2.1674 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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