Dexloxiglumide
Identification
- Generic Name
- Dexloxiglumide
- DrugBank Accession Number
- DB04856
- Background
Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist in phase III testing by Rottapharm in Europe only, as U.S. trials have been discontinued. As the D-isomer of loxiglumide, it retains all pharmacological properties of loxiglumide but is more potent.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 461.379
Monoisotopic: 460.153177494 - Chemical Formula
- C21H30Cl2N2O5
- Synonyms
- Dexloxiglumida
- Dexloxiglumide
- Dexloxiglumidum
- External IDs
- CR 2017
- CR-2017
Pharmacology
- Indication
For the treatment of Irritable Bowel Syndrome (IBS) and Gastroesophageal Reflux Disease (GERD).
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- Pharmacodynamics
Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist. In October 2003, following the completion of two phase III clinical studies involving dexloxiglumide in women with constipation-predominant irritable bowel syndrome (IBS), Forest Laboratories decided to discontinue development of the drug for this indication. The results of the studies showed that dexloxiglumide did not show statistically significant favorability over placebo. Rotta Research is continuing a phase III trial of a different design in Europe for the IBS indication and also for gastroesophogeal reflux disease.
- Mechanism of action
CCKA antagonists target receptors in the gastrointestinal system to increase gastric emptying and intestinal motility, as well as modulate intestinal sensitivity to distension.
Target Actions Organism UCholecystokinin receptor type A Not Available Humans - Absorption
Rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect.
- Volume of distribution
Not Available
- Protein binding
94-98%
- Metabolism
Cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxi-glumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Dexloxiglumide can be increased when it is combined with Abametapir. Abatacept The metabolism of Dexloxiglumide can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Dexloxiglumide. Acalabrutinib The metabolism of Dexloxiglumide can be decreased when combined with Acalabrutinib. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Dexloxiglumide. - Food Interactions
- Not Available
Categories
- Drug Categories
- Acids, Acyclic
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Fatty Acids
- Fatty Acids, Volatile
- Lipids
- Valerates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Glutamic acid and derivatives
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / Hippuric acids and derivatives / Alpha amino acid amides / 3-halobenzoic acids and derivatives / 4-halobenzoic acids and derivatives / Benzoyl derivatives / Dichlorobenzenes / Aryl chlorides / N-acyl amines / Tertiary carboxylic acid amides show 10 more
- Substituents
- 1,2-dichlorobenzene / 3-halobenzoic acid or derivatives / 4-halobenzoic acid or derivatives / Alpha-amino acid amide / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzamide / Benzenoid / Benzoic acid or derivatives show 26 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 69DY40RH9B
- CAS number
- 119817-90-2
- InChI Key
- QNQZBKQEIFTHFZ-GOSISDBHSA-N
- InChI
- 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
- IUPAC Name
- (4R)-4-[(3,4-dichlorophenyl)formamido]-4-[(3-methoxypropyl)(pentyl)carbamoyl]butanoic acid
- SMILES
- CCCCCN(CCCOC)C(=O)[C@@H](CCC(O)=O)NC(=O)C1=CC(Cl)=C(Cl)C=C1
References
- General References
- Persiani S, D'Amato M, Jakate A, Roy P, Wangsa J, Kapil R, Rovati LC: Pharmacokinetic profile of dexloxiglumide. Clin Pharmacokinet. 2006;45(12):1177-88. [Article]
- Maselli MA, Mennuni L: CCK1 receptor antagonist, dexloxiglumide: effects on human isolated gallbladder. Potential clinical applications. Minerva Gastroenterol Dietol. 2003 Sep;49(3):211-6. [Article]
- External Links
- PubChem Compound
- 65937
- PubChem Substance
- 175426866
- ChemSpider
- 59342
- ChEBI
- 135747
- ChEMBL
- CHEMBL550781
- ZINC
- ZINC000003801027
- Wikipedia
- Dexloxiglumide
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Irritable Bowel Syndrome (IBS) 1 2 Completed Treatment Dyspepsia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00555 mg/mL ALOGPS logP 3.23 ALOGPS logP 3.37 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 4.05 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 95.94 Å2 Chemaxon Rotatable Bond Count 14 Chemaxon Refractivity 117.01 m3·mol-1 Chemaxon Polarizability 47.86 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.5738 Blood Brain Barrier - 0.7306 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.8266 P-glycoprotein inhibitor I Non-inhibitor 0.5658 P-glycoprotein inhibitor II Non-inhibitor 0.6272 Renal organic cation transporter Non-inhibitor 0.868 CYP450 2C9 substrate Non-substrate 0.8529 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.788 CYP450 2C9 inhibitor Non-inhibitor 0.8266 CYP450 2D6 inhibitor Non-inhibitor 0.8319 CYP450 2C19 inhibitor Non-inhibitor 0.7627 CYP450 3A4 inhibitor Non-inhibitor 0.7224 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7843 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.9188 Biodegradation Not ready biodegradable 0.9931 Rat acute toxicity 2.1985 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9558 hERG inhibition (predictor II) Inhibitor 0.5705
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03dr-2632900000-7fa771bd76bcc7f5a3d2 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0133900000-d51b670d4d38ed3c9564 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0fdx-3930300000-507ce457153d52b94cb6 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0019100000-0b161395a675f680a946 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00dl-7911100000-e4b0efc4f58275c498f3 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-1519000000-07410a883958f859a53d Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 207.04906 predictedDeepCCS 1.0 (2019) [M+H]+ 209.40706 predictedDeepCCS 1.0 (2019) [M+Na]+ 215.85484 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Peptide binding
- Specific Function
- Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gas...
- Gene Name
- CCKAR
- Uniprot ID
- P32238
- Uniprot Name
- Cholecystokinin receptor type A
- Molecular Weight
- 47840.645 Da
References
- Persiani S, D'Amato M, Jakate A, Roy P, Wangsa J, Kapil R, Rovati LC: Pharmacokinetic profile of dexloxiglumide. Clin Pharmacokinet. 2006;45(12):1177-88. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- There are contradictory findings in the literature regarding this enzyme action. Some resources suggest CYP2B6 is involved[A15213], while others do not.[A185810]
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D'Amato M, Makovec F, Rovati LC: Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm Drug Dispos. 2004 May;25(4):163-76. [Article]
- Jakate AS, Roy P, Patel A, Abramowitz W, Persiani S, Wangsa J, Kapil R: Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide. Br J Clin Pharmacol. 2005 Nov;60(5):498-507. doi: 10.1111/j.1365-2125.2005.02465.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D'Amato M, Makovec F, Rovati LC: Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm Drug Dispos. 2004 May;25(4):163-76. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D'Amato M, Makovec F, Rovati LC: Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm Drug Dispos. 2004 May;25(4):163-76. [Article]
- Jakate AS, Roy P, Patel A, Abramowitz W, Persiani S, Wangsa J, Kapil R: Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide. Br J Clin Pharmacol. 2005 Nov;60(5):498-507. doi: 10.1111/j.1365-2125.2005.02465.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D'Amato M, Makovec F, Rovati LC: Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm Drug Dispos. 2004 May;25(4):163-76. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D'Amato M, Makovec F, Rovati LC: Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm Drug Dispos. 2004 May;25(4):163-76. [Article]
Drug created at October 19, 2007 00:07 / Updated at February 21, 2021 18:51