Page last updated: 2024-11-12

ulimorelin

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

Description

ulimorelin: ghrelin agonist; an 18-membered macrocycle containing 3 amide bonds and a secondary amine as well as 4 stereogenic centers; belongs to macrocyclic peptidomimetics [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID11526696
CHEMBL ID1963249
CHEMBL ID1923502
CHEBI ID177725
SCHEMBL ID804500
MeSH IDM0571671

Synonyms (32)

Synonym
(3r,6s,9r,12r)-6-cyclopropyl-12-[(4-luorophenyl)methyl]-3,8,9-trimethyl-2-oxa-5,8,11,14-tetrazabicyclo[16.4.0]docosa-1(22),18,20-triene-7,10,13-trione
CHEBI:177725
842131-33-3
ulimorelin
D09981
ulimorelin (usan/inn)
ulimorelin [usan:inn]
d-phenylalanine, (2s)-n-((2r)-2-(2-(3-aminopropyl)phenoxy)propyl)-2- cyclopropylglycyl-n-methyl-d-alanyl-4-fluoro-, (3-1)-lactam
unii-lgi67mcw2s
lgi67mcw2s ,
tzp 101
tzp-101
tzp-101 free base
CHEMBL1963249
CHEMBL1923502 ,
bdbm50359256
gtpl3535
(3r,6s,9r,12r)-6-cyclopropyl-12-[(4-fluorophenyl)methyl]-3,8,9-trimethyl-2-oxa-5,8,11,14-tetrazabicyclo[16.4.0]docosa-1(22),18,20-triene-7,10,13-trione
tzp101
SCHEMBL804500
ulimorelin [usan]
ulimorelin [who-dd]
ulimorelin [mi]
(2r,5s,8r,11r)-5-cyclopropyl-11-((4-fluorophenyl)methyl)-2,7,8-trimethyl- 2,3,4,5,7,8,10,11,13,14,15,16-dodecahydro-6h-1,4,7,10,13- benzoxatetraazacyclooctadecine-6,9,12-trione
ulimorelin [inn]
2h-1,4,7,10,13-benzoxatetraazacyclooctadecine-6,9,12(3h)-trione, 5-cyclopropyl-11- ((4-fluorophenyl)methyl)-4,5,7,8,10,11,13,14,15,16-decahydro-2,7,8-trimethyl-, (2r,5s,8r,11r)-
DTXSID00233139
DB12128
(2r,5s,8r,11r)-5-cyclopropyl-11-(4-fluorobenzyl)-2,7,8-trimethyl-4,5,7,8,10,11,13,14,15,16-decahydro-2h-benzo[q][1]oxa[4,7,10,13]tetraazacyclooctadecine-6,9,12(3h)-trione
HY-14903
Q21098959
CS-0003624

Research Excerpts

Overview

Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. It stimulates intestinal motility, but also reduces blood pressure in rodents and humans.

ExcerptReferenceRelevance
"Ulimorelin is a potent gastric prokinetic but lacks evidence of activity in the human colon, pointing to the stomach as the predominant site of action of ghrelin in humans; ClinicalTrials.gov NCT02993055."( The effects of ulimorelin, a ghrelin agonist, on liquid gastric emptying and colonic transit in humans.
Deane, AM; Doll, W; Harris, MS; James, J; Mair, S; Maurer, A; Sandefer, E; Wurtman, D, 2020
)
2.35
"Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. "( The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.
Brock, JA; Callaghan, B; Furness, JB; Kosari, S; Pustovit, RV; Rivera, LR; Thomas, H, 2014
)
2.07
"Ulimorelin (TZP101) is a ghrelin receptor agonist that stimulates intestinal motility, but also reduces blood pressure in rodents and humans and dilates blood vessels. "( Analysis of the ghrelin receptor-independent vascular actions of ulimorelin.
Broad, J; Brock, JA; Callaghan, B; Furness, JB; Sanger, GJ, 2015
)
2.1

Toxicity

ExcerptReferenceRelevance
" Subjects underwent continuous cardiac monitoring, 12-lead electrocardiograms, and assessment for orthostatic hypotension, injection site tolerability, vital signs, and adverse events during the 24-hour postdose period."( Ghrelin agonist (TZP-101): safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study.
Cummings, D; Gagnon, R; Kosutic, G; Lasseter, KC; Oliva, J; Pezzullo, JC; Shaughnessy, L; Wargin, W, 2008
)
0.35
" Safety was assessed with the use of standard assessments including adverse events and laboratory tests."( Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials.
Chamblin, B; McVey, D; Mondou, E; Pediconi, C; Quinn, J; Rousseau, F; Shaw, M, 2013
)
0.7
" Rates of serious adverse events were comparable across all treatment groups."( Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials.
Chamblin, B; McVey, D; Mondou, E; Pediconi, C; Quinn, J; Rousseau, F; Shaw, M, 2013
)
0.7

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic analysis revealed less than dose-proportional behavior of drug with low clearance (approximately 7 mL/h/kg), small volume of distribution (approximately 114 mL/kg), and half-life values of approximately 13 hours, which were independent of dose."( Ghrelin agonist (TZP-101): safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study.
Cummings, D; Gagnon, R; Kosutic, G; Lasseter, KC; Oliva, J; Pezzullo, JC; Shaughnessy, L; Wargin, W, 2008
)
0.35
" The objectives of this study was to assess pharmacokinetic parameters of TZP-101 after multiple- and single-dose administration to healthy subjects and patients with gastroparesis, respectively, and to determine the contribution of protein binding to its pharmacokinetic behaviour."( Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study.
Clohs, L; Ejskjaer, N; Gutierrez, M; Kosutic, G; Shaughnessy, L; St-Louis, C; Thomas, H; Wargin, W, 2009
)
0.35
"TZP-101 pharmacokinetic profiles were less than dose proportional in both healthy subjects and patients, most likely because of concentration-dependent protein binding."( Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study.
Clohs, L; Ejskjaer, N; Gutierrez, M; Kosutic, G; Shaughnessy, L; St-Louis, C; Thomas, H; Wargin, W, 2009
)
0.35
"The pharmacokinetic parameters of TZP-101 in patients with gastroparesis and healthy subjects are comparable and display a similar trend toward increased clearance at higher dose levels resulting in little accumulation of TZP-101 at high dose levels and after multiple dosing."( Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study.
Clohs, L; Ejskjaer, N; Gutierrez, M; Kosutic, G; Shaughnessy, L; St-Louis, C; Thomas, H; Wargin, W, 2009
)
0.35
" Early hits such as 1 (Ki=86 nM, EC50=134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization."( Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): Development of ulimorelin (TZP-101) from hit to clinic.
Beaubien, S; Beauchemin, S; Benakli, K; Bhat, S; Bhérer, P; Brassard, M; Foucher, L; Fraser, GL; Gagnon, R; Hoveyda, HR; Landry, A; Marsault, E; Mathieu, AP; Ouellet, L; Peng, X; Peterson, ML; Pinault, JF; Ramaseshan, M; Saint-Louis, C; Veber, DF; Vézina, M; Wang, Z, 2011
)
0.58

Bioavailability

ExcerptReferenceRelevance
" Compound 2 is 24% orally bioavailable in both rats and monkeys."( Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): Development of ulimorelin (TZP-101) from hit to clinic.
Beaubien, S; Beauchemin, S; Benakli, K; Bhat, S; Bhérer, P; Brassard, M; Foucher, L; Fraser, GL; Gagnon, R; Hoveyda, HR; Landry, A; Marsault, E; Mathieu, AP; Ouellet, L; Peng, X; Peterson, ML; Pinault, JF; Ramaseshan, M; Saint-Louis, C; Veber, DF; Vézina, M; Wang, Z, 2011
)
0.58

Dosage Studied

ExcerptRelevanceReference
" The aim of this study was to evaluate drug dosing and regional differences in drug activity between stomach and colon."( The effects of ulimorelin, a ghrelin agonist, on liquid gastric emptying and colonic transit in humans.
Deane, AM; Doll, W; Harris, MS; James, J; Mair, S; Maurer, A; Sandefer, E; Wurtman, D, 2020
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
oligopeptideA peptide containing a relatively small number of amino acids.
[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]

Protein Targets (1)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Growth hormone secretagogue receptor type 1Homo sapiens (human)EC50 (µMol)0.01100.00020.00870.0660AID1339932; AID1339956; AID711464
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Growth hormone secretagogue receptor type 1Homo sapiens (human)DC500.03200.03200.03200.0320AID1339957
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (47)

Processvia Protein(s)Taxonomy
G protein-coupled receptor signaling pathwayGrowth hormone secretagogue receptor type 1Homo sapiens (human)
spermatogenesisGrowth hormone secretagogue receptor type 1Homo sapiens (human)
learning or memoryGrowth hormone secretagogue receptor type 1Homo sapiens (human)
actin polymerization or depolymerizationGrowth hormone secretagogue receptor type 1Homo sapiens (human)
adult feeding behaviorGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to hormoneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
hormone-mediated signaling pathwayGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of norepinephrine secretionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
growth hormone secretionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to foodGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of appetiteGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of appetiteGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to follicle-stimulating hormoneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to estradiolGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of interleukin-1 beta productionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of interleukin-6 productionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of tumor necrosis factor productionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
cellular response to insulin stimulusGrowth hormone secretagogue receptor type 1Homo sapiens (human)
ghrelin secretionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of multicellular organism growthGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of hindgut contractionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of insulin-like growth factor receptor signaling pathwayGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of fatty acid metabolic processGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of insulin secretionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
decidualizationGrowth hormone secretagogue receptor type 1Homo sapiens (human)
insulin-like growth factor receptor signaling pathwayGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of inflammatory responseGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of synapse assemblyGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of transmission of nerve impulseGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of growth hormone secretionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to growth hormoneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
cellular response to lipopolysaccharideGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to dexamethasoneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of locomotion involved in locomotory behaviorGrowth hormone secretagogue receptor type 1Homo sapiens (human)
cellular response to thyroid hormone stimulusGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of neurotransmitter receptor localization to postsynaptic specialization membraneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
postsynaptic modulation of chemical synaptic transmissionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of postsynapse organizationGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of small intestinal transitGrowth hormone secretagogue receptor type 1Homo sapiens (human)
response to L-glutamateGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of sprouting angiogenesisGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of eating behaviorGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of small intestine smooth muscle contractionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
regulation of gastric motilityGrowth hormone secretagogue receptor type 1Homo sapiens (human)
positive regulation of vascular endothelial cell proliferationGrowth hormone secretagogue receptor type 1Homo sapiens (human)
cellular response to insulin-like growth factor stimulusGrowth hormone secretagogue receptor type 1Homo sapiens (human)
negative regulation of macrophage apoptotic processGrowth hormone secretagogue receptor type 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
growth hormone secretagogue receptor activityGrowth hormone secretagogue receptor type 1Homo sapiens (human)
G protein-coupled receptor activityGrowth hormone secretagogue receptor type 1Homo sapiens (human)
growth hormone-releasing hormone receptor activityGrowth hormone secretagogue receptor type 1Homo sapiens (human)
peptide hormone bindingGrowth hormone secretagogue receptor type 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (8)

Processvia Protein(s)Taxonomy
plasma membraneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
cell surfaceGrowth hormone secretagogue receptor type 1Homo sapiens (human)
neuron projectionGrowth hormone secretagogue receptor type 1Homo sapiens (human)
membrane raftGrowth hormone secretagogue receptor type 1Homo sapiens (human)
synaptic membraneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
Schaffer collateral - CA1 synapseGrowth hormone secretagogue receptor type 1Homo sapiens (human)
postsynapseGrowth hormone secretagogue receptor type 1Homo sapiens (human)
glutamatergic synapseGrowth hormone secretagogue receptor type 1Homo sapiens (human)
plasma membraneGrowth hormone secretagogue receptor type 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (4)

Assay IDTitleYearJournalArticle
AID711486Half life in rat2011Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7
Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
AID711491Oral bioavailability in rat2011Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7
Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
AID711464Agonist activity at ghrelin receptor2011Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7
Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
AID711484Clearance in rat2011Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7
Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's5 (21.74)29.6817
2010's17 (73.91)24.3611
2020's1 (4.35)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 21.77

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 Index21.77 (24.57)
Research Supply Index3.53 (2.92)
Research Growth Index4.71 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (21.77)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials10 (43.48%)5.53%
Reviews5 (21.74%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other8 (34.78%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]