Page last updated: 2024-11-06

dexloxiglumide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Dexloxiglumide is a potent and selective ghrelin receptor antagonist. It is being investigated as a potential treatment for obesity, diabetes, and other metabolic disorders. Ghrelin is a hormone that stimulates appetite and food intake, and dexloxiglumide blocks the action of ghrelin, potentially leading to reduced appetite and weight loss. The compound is currently in clinical trials to evaluate its safety and efficacy.'

dexloxiglumide: a CCK receptor antagonist; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID65937
CHEMBL ID550781
CHEBI ID135747
SCHEMBL ID366142
MeSH IDM0270576

Synonyms (35)

Synonym
gtpl889
(4r)-4-[(3,4-dichlorobenzoyl)amino]-5-(3-methoxypropyl-pentylamino)-5-oxopentanoic acid
cr-2017
dexloxiglumide
c21h30cl2n2o5
CHEBI:135747
AKOS000279054
(4r)-4-[(3,4-dichlorobenzoyl)amino]-5-[3-methoxypropyl(pentyl)amino]-5-oxopentanoic acid
CHEMBL550781
loxiglumide, (r)-
loxiglumide (r)-form
A804364
(4r)-4-[(3,4-dichlorobenzoyl)amino]-5-[3-methoxypropyl(pentyl)amino]-5-oxo-pentanoic acid
119817-90-2
69dy40rh9b ,
dexloxiglumide [inn]
dexloxiglumidum
unii-69dy40rh9b
dexloxiglumida
dexloxiglumida [inn-spanish]
dexloxiglumidum [inn-latin]
(r)-4-(3,4-dichlorobenzamido)-n-(3-methoxypropyl)-n-pentylglutaramic acid
(+)-loxiglumide
dexloxiglumide [who-dd]
loxiglumide (r)-form [mi]
DB04856
SCHEMBL366142
(r)-4-(3,4-dichlorobenzamido)-5-((3-methoxypropyl)(pentyl)amino)-5-oxopentanoic acid
DTXSID50152604
mfcd00866773
CS-0054881
Q5268340
AS-35102
HY-128878
pentanoic acid, 4-[(3,4-dichlorobenzoyl)amino]-5-[(3-methoxypropyl)pentylamino]-5-oxo-, (4r)-

Research Excerpts

Overview

Dexloxiglumide (DEX) is a cholecystokinin type-1 receptor antagonist under development for the treatment of constipation-predominant irritable bowel syndrome. It has demonstrated to revert the CCK mediated effects on gastrointestinal motility and sensitivity.

ExcerptReferenceRelevance
"Dexloxiglumide is a selective antagonist of the type 1 receptor of CCK, which has demonstrated to revert the CCK mediated effects on gastrointestinal motility and sensitivity. "( Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome.
Caballero, N; Serra, J, 2016
)
3.32
"Dexloxiglumide (DEX) is a cholecystokinin type-1 receptor antagonist under development for the treatment of constipation-predominant irritable bowel syndrome. "( Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450.
Cheung, YL; Cybulski, ZR; D'Amato, M; Hall, M; Holding, JD; Kapil, R; Makovec, F; Matthews, A; Persiani, S; Rovati, LC, 2004
)
2.12
"Dexloxiglumide is a new CCK(1) receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. "( Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide.
Abramowitz, W; Jakate, AS; Kapil, R; Patel, A; Persiani, S; Roy, P; Wangsa, J, 2005
)
2
"Dexloxiglumide is a potent and selective cholecystokinin type 1 (CCK1) receptor antagonist currently under development in a variety of diseases affecting the gastrointestinal tract such as gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), functional dyspepsia, constipation and gastric emptying disorders. "( Pharmacokinetic profile of dexloxiglumide.
D'Amato, M; Jakate, A; Kapil, R; Persiani, S; Rovati, LC; Roy, P; Wangsa, J, 2006
)
2.07

Effects

ExcerptReferenceRelevance
"Dexloxiglumide has demonstrated positive effects on important aspects of gastrointestinal function, like gastric emptying and gas tolerance, that deserves consideration in future studies. "( Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome.
Caballero, N; Serra, J, 2016
)
3.32

Actions

ExcerptReferenceRelevance
"Dexloxiglumide abolished the increase in gastric volume (DeltaV (ml): dexloxiglumide 17 (9), placebo 186 (49)) and dyspeptic symptoms (sum of scores: dexloxiglumide 24 (7), placebo 44 (19)) during duodenal lipid infusion."( Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia.
D'Amato, M; Feinle, C; Fried, M; Meier, O; Otto, B, 2001
)
1.03

Pharmacokinetics

Dexloxiglumide is a CCK-1 receptor antagonist. The safety and pharmacokinetic profile of the drug when the drug is administered as single and repeated doses in the dose range 100 - 400 mg provides the rationale for the choice of the treatment schedule (200 mg t)

ExcerptReferenceRelevance
" Dexloxiglumide plasma and urinary concentration, determined using validated HPLC methods with UV detection, were used for the pharmacokinetic analysis by standard noncompartmental methods."( Pharmacokinetics of dexloxiglumide after administration of single and repeat oral escalating doses in healthy young males.
Bishai, PM; D'Amato, M; Makovec, F; Persiani, S; Rovati, LC; Tavares, IA, 2002
)
1.55
" Comparable systemic exposure of EE and 17-DNE in the presence and absence of dexloxiglumide suggests that dexloxiglumide treatment is unlikely to interfere with the safety and efficacy of oral contraceptives based on the analysis of the resulting pharmacokinetic profile."( Effect of multiple-dose dexloxiglumide on the pharmacokinetics of oral contraceptives in healthy women.
Abramowitz, W; Jakate, AS; Kapil, R; Patel, A; Persiani, S; Roy, P; Wangsa, J, 2005
)
0.86
"To evaluate the effects of dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT) and symptoms in patients with constipation-predominant IBS (C-IBS); and to explore the influence of CCK-1 receptor polymorphisms on gut transit and the pharmacodynamic response to therapy."( Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study.
Burton, D; Camilleri, CE; Camilleri, M; Carlson, P; Cremonini, F; McKinzie, S; Thomforde, G; Urrutia, R; Zinsmeister, AR, 2005
)
0.92
" Analysis of covariance (ANCOVA) with age group and gender as factors and body weight as a covariate was performed on the dexloxiglumide pharmacokinetic parameters of peak plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC)."( The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender.
Abramowitz, W; Kapil, R; Nolting, A; Patel, A; Persiani, S; Roy, P; Wangsa, J, 2005
)
0.77
" Given the lack of age effects on the other pharmacokinetic parameters of dexloxiglumide, this limited difference is unlikely to be clinically relevant."( The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender.
Abramowitz, W; Kapil, R; Nolting, A; Patel, A; Persiani, S; Roy, P; Wangsa, J, 2005
)
0.79
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
"To compare COVs for bowel function with pharmacodynamic (PD) colonic transit geometric center (GC) as endpoints in lower FGID studies."( Pharmacodynamic and clinical endpoints for functional colonic disorders: statistical considerations.
Burton, D; Camilleri, M; Zinsmeister, AR, 2013
)
0.39

Bioavailability

ExcerptReferenceRelevance
" Dexloxiglumide is rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%."( Pharmacokinetic profile of dexloxiglumide.
D'Amato, M; Jakate, A; Kapil, R; Persiani, S; Rovati, LC; Roy, P; Wangsa, J, 2006
)
1.54
"5 h and a very high bioavailability (108 +/- 10%) in this species."( 3-[5-(3,4-Dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionate (JNJ-17156516), a novel, potent, and selective cholecystokinin 1 receptor antagonist: in vitro and in vivo pharmacological comparison with dexloxiglumide.
Barrett, TD; Breitenbucher, JG; Figueroa, K; Freedman, JM; Lagaud, G; Li, L; McClure, K; Moreno, V; Morton, MF; Prendergast, CE; Pyati, J; Rizzolio, M; Shankley, NP; Wu, X; Yan, W, 2007
)
0.52
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36

Dosage Studied

Dexloxiglumide Cmax occurred at 1.250 mg per 7-day phase, respectively) for 5 days (days 17-21) concurrently with either 200 mg dexloxglumide (3 times a day on days 17-20, followed by a single dose on day 21) or matching placebo.

ExcerptRelevanceReference
"250 mg per 7-day phase, respectively) for 5 days (days 17-21) concurrently with either 200 mg dexloxiglumide (3 times a day on days 17-20, followed by a single dose on day 21) or matching placebo during 2 consecutive 28-day OC dosing cycles."( Effect of multiple-dose dexloxiglumide on the pharmacokinetics of oral contraceptives in healthy women.
Abramowitz, W; Jakate, AS; Kapil, R; Patel, A; Persiani, S; Roy, P; Wangsa, J, 2005
)
0.85
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
glutamic acid derivativeAn amino acid derivative resulting from reaction of glutamic acid at the amino group or either of the carboxy groups, or from the replacement of any hydrogen by a heteroatom. The definition normally excludes peptides containing glutamic acid residues.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (27)

Assay IDTitleYearJournalArticle
AID1698004Fraction unbound in cynomolgus monkey plasma
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1698006Ratio of drug level in cynomolgus monkey blood to plasma administered through iv dosing by LC-MS/MS analysis
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1698002Intrinsic clearance in cryopreserved human hepatocytes at 1 uM measured up to 120 mins by LC-MS/MS analysis
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1698000Apparent permeability in dog MDCKII-LE cells at pH 7.4
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1698001Lipophilicity, log D of the compound at pH 7.4 by by shake flask method
AID1698011Fraction unbound in human plasma
AID1697999Dissociation constant, acidic pKa of compound measured up to 18 mins by capillary electrophoresis
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1698009Hepatic clearance in cynomolgus monkey at < 1 mg/kg, iv administered as cassette dosing
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1698007Ratio of drug level in human blood to plasma administered through iv dosing by LC-MS/MS analysis
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1698010Hepatic clearance in human administered through iv dosing
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1346912Human CCK1 receptor (Cholecystokinin receptors)2007The Journal of pharmacology and experimental therapeutics, Nov, Volume: 323, Issue:2
3-[5-(3,4-Dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionate (JNJ-17156516), a novel, potent, and selective cholecystokinin 1 receptor antagonist: in vitro and in vivo pharmacological comparison with dexloxiglumide.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (32)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's2 (6.25)18.2507
2000's22 (68.75)29.6817
2010's7 (21.88)24.3611
2020's1 (3.13)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 27.48

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index27.48 (24.57)
Research Supply Index3.85 (2.92)
Research Growth Index5.54 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (27.48)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials11 (31.43%)5.53%
Reviews6 (17.14%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other18 (51.43%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]