Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H19ClFNO4S |
Molecular Weight | 435.896 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(=O)(=O)C1=C2N(CC3=CC=C(Cl)C=C3)C4=C(CC[C@@H]4CC(O)=O)C2=CC(F)=C1
InChI
InChIKey=NXFFJDQHYLNEJK-CYBMUJFWSA-N
InChI=1S/C21H19ClFNO4S/c1-29(27,28)18-10-15(23)9-17-16-7-4-13(8-19(25)26)20(16)24(21(17)18)11-12-2-5-14(22)6-3-12/h2-3,5-6,9-10,13H,4,7-8,11H2,1H3,(H,25,26)/t13-/m1/s1
Molecular Formula | C21H19ClFNO4S |
Molecular Weight | 435.896 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdfCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17300164 | https://www.ncbi.nlm.nih.gov/pubmed/19748656
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdf
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17300164 | https://www.ncbi.nlm.nih.gov/pubmed/19748656
Laropiprant is a drug, which was used in combination with nicotinic acid (also known as niacin) and was known under tradename: tredaptive. Tredaptive was indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia. The marketing authorisation for Tredaptive has been withdrawn at the request of the marketing-authorisation holder due to increases in side effects with no cardiovascular benefit. Laropiprant is a selective antagonist of the prostaglandin D(2) (PGD(2)) receptor subtype 1 (DP1). It also has the affinity to interact with thromboxane A2 receptor (TP), although it is approximately 190-fold less potent when compared to DP1. Activation of TP has been shown to induce platelet aggregation in vitro, whereas activation of human platelet DP1 inhibits platelet aggregation. These in vitro data indicate that laropiprant may alter platelet function either by enhancement of platelet reactivity through DP1 antagonism or by inhibition of platelet aggregation through TP antagonism. Also were clinical trials phase II for the laropiprant alone, there were shown, that drug did not demonstrate efficacy in asthmatic patients or patients with allergic rhinitis.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4427 |
0.09 nM [IC50] | ||
Target ID: Q13258 Gene ID: 5729.0 Gene Symbol: PTGDR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17300164 |
0.57 nM [Ki] | ||
Target ID: CHEMBL4427 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17300164 |
0.57 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | Tredaptive Approved UseTredaptive is indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia: who are treated with a statin and could benefit from having Tredaptive added to their regimen, in whom a statin is considered inappropriate or not tolerated |
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Palliative | Tredaptive Approved UseTredaptive is indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia: who are treated with a statin and could benefit from having Tredaptive added to their regimen, in whom a statin is considered inappropriate or not tolerated |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Gateways to clinical trials. | 2007 Dec |
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Targeting multiple dyslipidemias with fixed combinations--focus on extended release niacin and simvastatin. | 2008 |
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Gateways to clinical trials. | 2008 Apr |
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Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia. | 2008 Dec |
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Gateways to clinical trials. July-August 2008. | 2008 Jul-Aug |
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Gateways to clinical trials. | 2008 Jun |
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Pharmacokinetics, pharmacodynamics, and safety of a prostaglandin D2 receptor antagonist. | 2008 Jun |
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Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. | 2008 Mar 1 |
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Gateways to clinical trials. | 2008 May |
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Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors. | 2008 Nov |
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Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia. | 2009 |
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Flushing profile of extended-release niacin/laropiprant at initiation of therapy in Asian lipid clinic patients. | 2009 |
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Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin. | 2009 |
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Effects of aspirin when added to the prostaglandin D2 receptor antagonist laropiprant on niacin-induced flushing symptoms. | 2009 Apr |
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Nephropathy and other topics. | 2009 Aug |
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Extended-release niacin (nicotinic acid)/laropiprant. | 2009 Aug 20 |
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Laropiprant in combination with extended-release niacin does not alter urine 11-dehydrothromboxane B2, a marker of in vivo platelet function, in healthy, hypercholesterolemic, and diabetic subjects. | 2009 Dec |
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Current strategies and recent advances in the therapy of hypercholesterolemia. | 2009 Dec 29 |
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Blood pressure-lowering effects of extended-release niacin alone and extended-release niacin/laropiprant combination: a post hoc analysis of a 24-week, placebo-controlled trial in dyslipidemic patients. | 2009 Jan |
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Niacin: an old drug rejuvenated. | 2009 Jan |
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Does nicotinic acid (niacin) lower blood pressure? | 2009 Jan |
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Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. | 2009 Jul 1 |
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Lipid-modifying efficacy of extended release niacin/laropiprant in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia. | 2009 May-Jun |
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Influence of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the pharmacokinetics and pharmacodynamics of warfarin. | 2009 May-Jun |
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Mechanisms of flushing due to niacin and abolition of these effects. | 2009 Nov |
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Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis. | 2009 Nov |
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Effect of laropiprant, a PGD2 receptor 1 antagonist, on estradiol and norgestimate pharmacokinetics after oral contraceptive administration in women. | 2009 Nov-Dec |
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High-density lipoprotein cholesterol: current perspective for clinicians. | 2009 Oct-Nov |
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The mechanism and mitigation of niacin-induced flushing. | 2009 Sep |
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Pharmacokinetics of laropiprant and glucuronide metabolite in patients with severe renal insufficiency. | 2009 Sep-Oct |
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Effects of laropiprant, a selective prostaglandin D(2) receptor 1 antagonist, on the pharmacokinetics of rosiglitazone. | 2009 Winter |
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Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia. | 2010 |
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Effects of extended release niacin/laropiprant, laropiprant, extended release niacin and placebo on platelet aggregation and bleeding time in healthy subjects. | 2010 |
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Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. | 2010 Apr |
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Management of hypertriglyceridemia in the diabetic patient. | 2010 Aug |
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Treatment of dyslipidemia in patients with type 2 diabetes. | 2010 Dec 20 |
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Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors. | 2010 Jan |
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Niacin, an old drug with new perspectives for the management of dyslipidaemia. | 2010 Jan-Feb |
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High density lipoproteins-based therapies for cardiovascular disease. | 2010 Jul |
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[Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: non-pharmacological and pharmacological approaches]. | 2010 Jul |
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Laropiprant plus niacin for dyslipidemia and prevention of cardiovascular disease. | 2010 Jul |
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Effects of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the steady-state pharmacokinetics of digoxin in healthy adult subjects. | 2010 Jul |
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Niacin and laropiprant. | 2010 Jun |
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A new paradigm for managing dyslipidemia with combination therapy: laropiprant + niacin + simvastatin. | 2010 Mar |
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Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia. | 2010 May |
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Single therapeutic and supratherapeutic doses of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, do not prolong the QTcF interval in healthy volunteers. | 2010 Nov |
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Efficacy and tolerability of extended-release niacin/laropiprant in dyslipidemic patients with metabolic syndrome. | 2010 Nov-Dec |
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HDL and LDL as therapeutic targets for cardiovascular disease prevention: the possible role of niacin. | 2010 Oct |
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Low high-density lipoprotein cholesterol: current status and future strategies for management. | 2010 Oct 29 |
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Recent advances in preventing cardiovascular disorders by managing lipid levels. | 2010 Sep 8 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00664287
niacin/laropiprant 1 g/20 mg daily. After 4 weeks, niacin/laropiprant will be increased to 2 g/40 mg for remainder of study.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22870195
In vitro treatment of platelets with laropiprant (1 µmol/L) prevented the inhibitory effects of PGD(2) on platelet function, i.e. platelet aggregation, Ca(2+) flux, P-selectin expression, activation of glycoprotein IIb/IIIa and thrombus formation. At higher concentrations, 10 µmol/L laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation, Ca(2+) flux, P-selectin expression, and activation of glycoprotein IIb/IIIa.
Substance Class |
Chemical
Created
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admin
on
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Record UNII |
G7N11T8O78
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Record Status |
Validated (UNII)
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C26170
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
Functional Assay cAMP Accumulation in platelets
IC50
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EXCRETED UNCHANGED |
URINE
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TARGET -> INHIBITOR |
Binding
Ki
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MAJOR
FECAL
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METABOLITE -> PARENT |
MAJOR
URINE
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
PLASMA
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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P.O. ADMINISTRATION |
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