LAROPIPRANT

Possibly Marketed Outside US

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 Search

SMILES

CS(=O)(=O)C1=CC(F)=CC2=C1N(CC3=CC=C(Cl)C=C3)C4=C2CC[C@@H]4CC(O)=O

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 The marketing authorisation for Tredaptive has been withdrawn at the request of the marketing-authorisation holder due to increases in side effects with no cardiovascular benefit.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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostanoid DP receptor 16 Target ID: CHEMBL4427 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17300164	Antagonist 2849		0.57 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Hypercholesterolemia 51 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdf	Palliative	Withdrawn	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
Mixed dyslipidemia 8 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdf	Palliative	Withdrawn	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
Allergic rhinitis 104 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19748656	Primary	Phase II 1147	Unknown Approved Use Unknown
Asthma 244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19748656	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.34 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17431030/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: CLARITHROMYCIN	CLARITHROMYCIN	LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.06 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.35 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.73 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.18 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
10.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17431030/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: CLARITHROMYCIN	CLARITHROMYCIN	LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
19.69 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12.46 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
33.3 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
15.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: CLARITHROMYCIN	CLARITHROMYCIN	LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20337634/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
26 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19433974/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
16.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20484612/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROPIPRANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22607011/			LAROPIPRANT plasma	Homo sapiens

Doses

Dose	Population	Adverse events
900 mg single, oral Highest studied dose Dose: 900 mg Route: oral Route: single Dose: 900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/	Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/
450 mg 1 times / day multiple, oral Studied dose Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/	Sources: https://pubmed.ncbi.nlm.nih.gov/17882161/

PubMed

Title	Date	PubMed
Treatment of dyslipidemia in patients with type 2 diabetes.	2010-12-20	21172030
Single therapeutic and supratherapeutic doses of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, do not prolong the QTcF interval in healthy volunteers.	2010-11	20107202
Low high-density lipoprotein cholesterol: current status and future strategies for management.	2010-10-29	21127701
HDL and LDL as therapeutic targets for cardiovascular disease prevention: the possible role of niacin.	2010-10	20739153
Recent advances in preventing cardiovascular disorders by managing lipid levels.	2010-09-08	21173859
Management of hypertriglyceridemia in the diabetic patient.	2010-08	20532703
High density lipoproteins-based therapies for cardiovascular disease.	2010-07	21187875
[Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: non-pharmacological and pharmacological approaches].	2010-07	20842907
Laropiprant plus niacin for dyslipidemia and prevention of cardiovascular disease.	2010-07	20518616
Effects of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the steady-state pharmacokinetics of digoxin in healthy adult subjects.	2010-07	20197486
Niacin and laropiprant.	2010-06	20571606
Efficacy and tolerability of extended-release niacin/laropiprant in dyslipidemic patients with metabolic syndrome.	2010-05-24	21122699
Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia.	2010-05	20518948
Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.	2010-04-15	20421916
Niacin, an old drug with new perspectives for the management of dyslipidaemia.	2010-04-09	20373594
Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial.	2010-04	20299362
A new paradigm for managing dyslipidemia with combination therapy: laropiprant + niacin + simvastatin.	2010-03	20141348
Nicotinic acid + larodiorant. Laropiprant adds its own adverse effects.	2010-02	20455330
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.	2010-01	19825813
Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.	2010	21701618
Effects of extended release niacin/laropiprant, laropiprant, extended release niacin and placebo on platelet aggregation and bleeding time in healthy subjects.	2010	20163197
Current strategies and recent advances in the therapy of hypercholesterolemia.	2009-12-29	20129365
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.	2009-12	19833861
Effect of laropiprant, a PGD2 receptor 1 antagonist, on estradiol and norgestimate pharmacokinetics after oral contraceptive administration in women.	2009-11-27	19940609
Mechanisms of flushing due to niacin and abolition of these effects.	2009-11	19878384
Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis.	2009-11	19748656
The mechanism and mitigation of niacin-induced flushing.	2009-09	19691622
Extended-release niacin (nicotinic acid)/laropiprant.	2009-08-20	19678716
Nephropathy and other topics.	2009-08	19638520
Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease.	2009-07-01	19576324
Influence of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the pharmacokinetics and pharmacodynamics of warfarin.	2009-05-21	19454860
Pharmacokinetics of laropiprant and glucuronide metabolite in patients with severe renal insufficiency.	2009-05-13	19433974
Effects of aspirin when added to the prostaglandin D2 receptor antagonist laropiprant on niacin-induced flushing symptoms.	2009-04	19246721
High-density lipoprotein cholesterol: current perspective for clinicians.	2009-02-26	19240106
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.	2009-01	19243712
Niacin: an old drug rejuvenated.	2009-01	19080727
Does nicotinic acid (niacin) lower blood pressure?	2009-01	19054161
Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia.	2009	20016845
Effects of laropiprant, a selective prostaglandin D(2) receptor 1 antagonist, on the pharmacokinetics of rosiglitazone.	2009	19903187
Flushing profile of extended-release niacin/laropiprant at initiation of therapy in Asian lipid clinic patients.	2009	19602880
Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin.	2009	19436666
Lipid-modifying efficacy of extended release niacin/laropiprant in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia.	2008-12-09	21291812
Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.	2008-12	19166443
Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors.	2008-11	19031552
Gateways to clinical trials. July-August 2008.	2008-10-14	18850047
Nicotinic acid: recent developments.	2008-07	18520725
Gateways to clinical trials.	2008-06	18806898
Gateways to clinical trials.	2008-05	18773127
Gateways to clinical trials.	2008-04	18597009
Targeting multiple dyslipidemias with fixed combinations--focus on extended release niacin and simvastatin.	2008	19183748

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 18:23:19 GMT 2025` Edited by `admin` on `Mon Mar 31 18:23:19 GMT 2025`
Record UNII	G7N11T8O78
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LAROPIPRANT [EMA EPAR]

Preferred Name

English

LAROPIPRANT

Official 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