U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of LAROPIPRANT

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

HIDE SMILES / InChI

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

Description
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 The marketing authorisation for Tredaptive has been withdrawn at the request of the marketing-authorisation holder due to increases in side effects with no cardiovascular benefit.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.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.09 nM [IC50]
Target ID: Q13258
Gene ID: 5729.0
Gene Symbol: PTGDR
Target Organism: Homo sapiens (Human)
0.57 nM [Ki]
0.57 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Tredaptive

Approved Use

Tredaptive 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
Palliative
Tredaptive

Approved Use

Tredaptive 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
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Gateways to clinical trials.
2007 Dec
Targeting multiple dyslipidemias with fixed combinations--focus on extended release niacin and simvastatin.
2008
Gateways to clinical trials.
2008 Apr
Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.
2008 Dec
Gateways to clinical trials. July-August 2008.
2008 Jul-Aug
Gateways to clinical trials.
2008 Jun
Pharmacokinetics, pharmacodynamics, and safety of a prostaglandin D2 receptor antagonist.
2008 Jun
Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia.
2008 Mar 1
Gateways to clinical trials.
2008 May
Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors.
2008 Nov
Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia.
2009
Flushing profile of extended-release niacin/laropiprant at initiation of therapy in Asian lipid clinic patients.
2009
Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin.
2009
Effects of aspirin when added to the prostaglandin D2 receptor antagonist laropiprant on niacin-induced flushing symptoms.
2009 Apr
Nephropathy and other topics.
2009 Aug
Extended-release niacin (nicotinic acid)/laropiprant.
2009 Aug 20
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
Current strategies and recent advances in the therapy of hypercholesterolemia.
2009 Dec 29
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
Niacin: an old drug rejuvenated.
2009 Jan
Does nicotinic acid (niacin) lower blood pressure?
2009 Jan
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
Lipid-modifying efficacy of extended release niacin/laropiprant in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia.
2009 May-Jun
Influence of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the pharmacokinetics and pharmacodynamics of warfarin.
2009 May-Jun
Mechanisms of flushing due to niacin and abolition of these effects.
2009 Nov
Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis.
2009 Nov
Effect of laropiprant, a PGD2 receptor 1 antagonist, on estradiol and norgestimate pharmacokinetics after oral contraceptive administration in women.
2009 Nov-Dec
High-density lipoprotein cholesterol: current perspective for clinicians.
2009 Oct-Nov
The mechanism and mitigation of niacin-induced flushing.
2009 Sep
Pharmacokinetics of laropiprant and glucuronide metabolite in patients with severe renal insufficiency.
2009 Sep-Oct
Effects of laropiprant, a selective prostaglandin D(2) receptor 1 antagonist, on the pharmacokinetics of rosiglitazone.
2009 Winter
Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.
2010
Effects of extended release niacin/laropiprant, laropiprant, extended release niacin and placebo on platelet aggregation and bleeding time in healthy subjects.
2010
Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial.
2010 Apr
Management of hypertriglyceridemia in the diabetic patient.
2010 Aug
Treatment of dyslipidemia in patients with type 2 diabetes.
2010 Dec 20
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
Niacin, an old drug with new perspectives for the management of dyslipidaemia.
2010 Jan-Feb
High density lipoproteins-based therapies for cardiovascular disease.
2010 Jul
[Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: non-pharmacological and pharmacological approaches].
2010 Jul
Laropiprant plus niacin for dyslipidemia and prevention of cardiovascular disease.
2010 Jul
Effects of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the steady-state pharmacokinetics of digoxin in healthy adult subjects.
2010 Jul
Niacin and laropiprant.
2010 Jun
A new paradigm for managing dyslipidemia with combination therapy: laropiprant + niacin + simvastatin.
2010 Mar
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
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
Efficacy and tolerability of extended-release niacin/laropiprant in dyslipidemic patients with metabolic syndrome.
2010 Nov-Dec
HDL and LDL as therapeutic targets for cardiovascular disease prevention: the possible role of niacin.
2010 Oct
Low high-density lipoprotein cholesterol: current status and future strategies for management.
2010 Oct 29
Recent advances in preventing cardiovascular disorders by managing lipid levels.
2010 Sep 8
Patents

Sample Use Guides

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 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
by admin
on Fri Dec 15 16:15:40 GMT 2023
Edited
by admin
on Fri Dec 15 16:15:40 GMT 2023
Record UNII
G7N11T8O78
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROPIPRANT
DASH   EMA EPAR   INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
LAROPIPRANT [EMA EPAR]
Common Name English
LAROPIPRANT [MART.]
Common Name English
Laropiprant [WHO-DD]
Common Name English
LAROPIPRANT [MI]
Common Name English
CORDAPTIVE
Brand Name English
LAROPIPRANT [USAN]
Common Name English
laropiprant [INN]
Common Name English
CYCLOPENT(B)INDOLE-3-ACETIC ACID, 4-((4-CHLOROPHENYL)METHYL)-7-FLUORO-1,2,3,4-TETRAHYDRO-5-(METHYLSULFONYL)-, (3R)-
Common Name English
(-)-((3R)-4-(4-CHLOROBENZYL)-7-FLUORO-5-(METHYLSULFONYL)-1,2,3,4-TETRAHYDROCYCLOPENTA(B)INDOL-3-YL)ACETIC ACID
Systematic Name English
MK-0524
Code English
Classification Tree Code System Code
NCI_THESAURUS C26170
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
Code System Code Type Description
MERCK INDEX
m6696
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY Merck Index
MESH
C518174
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
PUBCHEM
9867642
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
NCI_THESAURUS
C87372
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
EPA CompTox
DTXSID60205756
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
SMS_ID
100000089640
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
DRUG CENTRAL
4326
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
CAS
571170-77-9
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
USAN
RR-81
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
FDA UNII
G7N11T8O78
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
WIKIPEDIA
LAROPIPRANT
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
DRUG BANK
DB11629
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
INN
8855
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
ChEMBL
CHEMBL426559
Created by admin on Fri Dec 15 16:15:40 GMT 2023 , Edited by admin on Fri Dec 15 16:15:40 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Functional Assay cAMP Accumulation in platelets
IC50
EXCRETED UNCHANGED
URINE
TARGET -> INHIBITOR
Binding
Ki
EXCRETED UNCHANGED
MAJOR
FECAL
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC P.O. ADMINISTRATION