Laropiprant
drugOn this page
Also known as CordaptiveMK-0524
Summary
Laropiprant (CHEMBL426559) is an approved small molecule targeting PTGDR and TBXA2R; indicated across 8 conditions including familial hypercholesterolemia and type 2 diabetes mellitus.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- Targets: 2 (PTGDR, TBXA2R)
- Indications: 8 conditions
- Clinical trials: 16
- Chemistry: 435.9 Da · C21H19ClFNO4S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL426559 |
| Name | Laropiprant |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 9867642 |
| Molecular formula | C21H19ClFNO4S |
| Molecular weight | 435.9 |
| InChIKey | NXFFJDQHYLNEJK-CYBMUJFWSA-N |
SMILES: CS(=O)(=O)C1=CC(=CC2=C1N(C3=C2CC[C@@H]3CC(=O)O)CC4=CC=C(C=C4)Cl)F
IUPAC name: 2-[(3R)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1H-cyclopenta[b]indol-3-yl]acetic acid
Also known as: Cordaptive, Laropiprant, MK-0524, LAROPIPRANT, laropiprant
Parent form; salt/anhydrous children: CHEMBL218415, CHEMBL375527
Patent coverage: 192 distinct patent families (541 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 539 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| PTGDR | DP1 receptor | Antagonist | 10.1 | 0.4% | Q13258 |
| TBXA2R | TP receptor | Antagonist | 6.1 | 0.2% | P21731 |
Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Prostaglandin E2 receptor EP1 subtype, Prostaglandin E2 receptor EP2 subtype, Prostaglandin F2-alpha receptor, Prostacyclin receptor, Thromboxane A2 receptor, D(3) dopamine receptor, 3’,5’-cyclic-AMP phosphodiesterase 4A, 3’,5’-cyclic-AMP phosphodiesterase 4D, Prostaglandin E2 receptor EP3 subtype, Prostaglandin D2 receptor.
Bioactivity
ChEMBL activities: 21 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| PTGDR | 10.52 | Kd | 0.03 | nM | CHEMBL_ACT_1818039 |
| PTGDR | 10.05 | IC50 | 0.09 | nM | CHEMBL_ACT_1818008 |
| PTGDR | 9.24 | Ki | 0.57 | nM | CHEMBL_ACT_1817973 |
| PTGDR | 8.85 | IC50 | 1.4 | nM | CHEMBL_ACT_1818046 |
| TBXA2R | 8.53 | Ki | 2.95 | nM | CHEMBL_ACT_1817977 |
| PTGDR | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_1818012 |
| TBXA2R | 8.24 | AC50 | 5.7 | nM | CHEMBL_ACT_25197491 |
| TBXA2R | 7.96 | Kd | 10.9 | nM | CHEMBL_ACT_1818040 |
| PTGER2 | 6.87 | Ki | 136 | nM | CHEMBL_ACT_1817985 |
| TBXA2R | 6.77 | AC50 | 170 | nM | CHEMBL_ACT_25197623 |
| TSPO | 6.54 | Ki | 286.4 | nM | CHEMBL_ACT_25741155 |
| TBXA2R | 6.42 | AC50 | 380 | nM | CHEMBL_ACT_25154849 |
| PTGDR2 | 6.13 | Ki | 745 | nM | CHEMBL_ACT_1818045 |
| TBXA2R | 6.11 | IC50 | 770 | nM | CHEMBL_ACT_1818016 |
| PTGER3 | 6.05 | Ki | 892 | nM | CHEMBL_ACT_1817989 |
| PDE4A | 6.02 | AC50 | 960 | nM | CHEMBL_ACT_25206848 |
| DRD3 | 5.95 | Ki | 1122 | nM | CHEMBL_ACT_25741154 |
| PTGER1 | 5.94 | Ki | 1160 | nM | CHEMBL_ACT_1817981 |
| PDE4D | 5.6 | AC50 | 2500 | nM | CHEMBL_ACT_25184881 |
| PTGIR | 5.18 | Ki | 6628 | nM | CHEMBL_ACT_1818001 |
| PTGFR | 5 | Ki | 9991 | nM | CHEMBL_ACT_1817997 |
Target pathways
Aggregated over 2 target gene(s): PTGDR, TBXA2R.
Top Reactome pathways
14 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Prostanoid ligand receptors | 2 | PTGDR, TBXA2R |
| Hemostasis | 1 | TBXA2R |
| Signal Transduction | 1 | TBXA2R |
| Signaling by GPCR | 1 | TBXA2R |
| Class A/1 (Rhodopsin-like receptors) | 1 | TBXA2R |
| GPCR downstream signalling | 1 | TBXA2R |
| Eicosanoid ligand-binding receptors | 1 | TBXA2R |
| Signal amplification | 1 | TBXA2R |
| G alpha (q) signalling events | 1 | TBXA2R |
| G alpha (12/13) signalling events | 1 | TBXA2R |
| G alpha (s) signalling events | 1 | PTGDR |
| Thromboxane signalling through TP receptor | 1 | TBXA2R |
| GPCR ligand binding | 1 | TBXA2R |
| Platelet activation, signaling and aggregation | 1 | TBXA2R |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| inflammatory response | 2 |
| G protein-coupled receptor signaling pathway | 2 |
| positive regulation of cytosolic calcium ion concentration | 2 |
| signal transduction | 2 |
| male sex determination | 1 |
| sleep | 1 |
| mast cell degranulation | 1 |
| adenosine metabolic process | 1 |
| cellular response to prostaglandin D stimulus | 1 |
| smooth muscle contraction | 1 |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 1 |
| response to nutrient | 1 |
| response to xenobiotic stimulus | 1 |
| positive regulation of blood coagulation | 1 |
| response to testosterone | 1 |
Indications & clinical
Indications
8 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| familial hypercholesterolemia | 3 | MONDO:0005439 | EFO:0004911 |
| type 2 diabetes mellitus | 3 | MONDO:0005148 | MONDO:0005148 |
| hyperlipidemia | 3 | MONDO:0021187 | MONDO:0021187 |
| rosacea | 1 | MONDO:0006604 | EFO:1000760 |
4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 16.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 7 |
| PHASE3 | 5 |
| PHASE1 | 4 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01010516 | PHASE4 | UNKNOWN | Comparison of High-Dose Rosuvastatin Versus Low Statin Dose Plus Fenofibrate Versus Low Statin Dose Plus Niacin in the Treatment of Mixed Hyperlipidemia |
| NCT01054508 | PHASE4 | COMPLETED | Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers |
| NCT01126073 | PHASE4 | COMPLETED | Niacin/Laropiprant and Endothelial Function |
| NCT01239992 | PHASE4 | TERMINATED | Effect of Niacin/Laropiprant on Postprandial Lipoprotein Metabolism in Patients With Dyslipoproteinemia |
| NCT01308203 | PHASE4 | TERMINATED | Lipid Efficacy of the Extended Release Niacin/Laropiprant Combination in Patients With Cardiovascular Disease |
| NCT01321034 | PHASE4 | COMPLETED | Effect of Niacin in the Lipoprotein (a) Concentration |
| NCT01683656 | PHASE4 | TERMINATED | ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART |
| NCT00461630 | PHASE3 | COMPLETED | Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE |
| NCT00485758 | PHASE3 | COMPLETED | Extended Niacin/Laropiprant in Patients With Type 2 Diabetes (0524A-069) |
| NCT00536510 | PHASE3 | COMPLETED | Effect of MK0524A on Cholesterol Levels (0524A-048) |
| NCT01294683 | PHASE3 | TERMINATED | A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118) |
| NCT01335997 | PHASE3 | TERMINATED | Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143) |
| NCT00618995 | PHASE1 | COMPLETED | A Study to Evaluate the Effects of ER Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites (0524A-079)(COMPLETED) |
| NCT00769132 | PHASE1 | COMPLETED | A Study to Evaluate the Effects of Extended Release (ER) Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites in Subjects With High Cholesterol (0524A-075)(COMPLETED) |
| NCT01012219 | PHASE1 | COMPLETED | A Study to Evaluate the Effects of Laropiprant on the Antiplatelet Effects of Clopidogrel and Aspirin in Combination (MK-0524A-114)(COMPLETED) |
| NCT01451619 | PHASE1 | COMPLETED | A Study of Laropiprant (MK-0524) in Participants With Moderate to Severe Erythematotelangiectatic Rosacea (MK-0524-155) |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
292 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| DINOPROST | ChEMBL + PubChem | Phase 4 (approved) | PTGDR, TBXA2R |
| dinoprostone | ChEMBL + PubChem | Phase 4 (approved) | PTGDR, TBXA2R |
| RAMATROBAN | ChEMBL | Phase 4 (approved) | PTGDR, TBXA2R |
| SELEXIPAG | ChEMBL | Phase 4 (approved) | PTGDR, TBXA2R |
| Cloprostenol | ChEMBL + PubChem | Phase 2 (approved) | PTGDR, TBXA2R |
| BI-671800 | ChEMBL | Phase 2 | PTGDR, TBXA2R |
| LASELIPAG | ChEMBL | Phase 2 | PTGDR, TBXA2R |
| Belzutifan | PubChem | Approved | PTGDR, TBXA2R |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| ESTRADIOL VALERATE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| ILOPROST | ChEMBL + PubChem | Phase 4 (approved) | PTGDR |
| OLANZAPINE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| POMALIDOMIDE | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| RIFAMPIN | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | TBXA2R |
| ACETYLCHOLINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| AMSACRINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | TBXA2R |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | TBXA2R |
| AXITINIB | ChEMBL | Phase 4 (approved) | TBXA2R |
| BECLOMETHASONE DIPROPIONATE | ChEMBL | Phase 4 (approved) | TBXA2R |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| BENZIODARONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | TBXA2R |
| BITHIONOL | ChEMBL | Phase 4 (approved) | TBXA2R |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| CABOZANTINIB | ChEMBL | Phase 4 (approved) | TBXA2R |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | TBXA2R |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | TBXA2R |
| CERIVASTATIN | ChEMBL | Phase 4 (approved) | TBXA2R |
| CHLORMADINONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | TBXA2R |
| CHOLECALCIFEROL | ChEMBL | Phase 4 (approved) | TBXA2R |
| CICLOPIROX | ChEMBL | Phase 4 (approved) | TBXA2R |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | TBXA2R |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | TBXA2R |
| COBIMETINIB | ChEMBL | Phase 4 (approved) | TBXA2R |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | TBXA2R |
| DELAVIRDINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| DEOXYCHOLIC ACID | ChEMBL | Phase 4 (approved) | TBXA2R |
| DEXAMETHASONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| DEXTROTHYROXINE | ChEMBL | Phase 4 (approved) | TBXA2R |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | TBXA2R |
| DOXAZOSIN | ChEMBL | Phase 4 (approved) | TBXA2R |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | TBXA2R |
| DRONEDARONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| DUVELISIB | ChEMBL | Phase 4 (approved) | TBXA2R |
| DYDROGESTERONE | ChEMBL | Phase 4 (approved) | TBXA2R |
| ENASIDENIB | ChEMBL | Phase 4 (approved) | TBXA2R |
| ENOXACIN | ChEMBL | Phase 4 (approved) | TBXA2R |
Related Atlas pages
- Genes: PTGDR, TBXA2R
- Diseases: familial hypercholesterolemia, type 2 diabetes mellitus, hyperlipidemia
- Drugs: Dinoprost, dinoprostone, Ramatroban, Selexipag, Belzutifan, Clozapine, Desloratadine, Dihydroergotamine, Estradiol Valerate, Iloprost, Olanzapine, Pimavanserin, Pomalidomide, Regorafenib, Rifampin, Tegaserod, Acetylcholine, Amitriptyline, Amlodipine, Amsacrine, Aripiprazole, Astemizole, Axitinib, Beclomethasone Dipropionate, Benzbromarone, Benziodarone, Bexarotene, Bithionol, Bromocriptine, Bromodiphenhydramine, Cabozantinib, Candesartan Cilexetil, Cannabidiol, Cerivastatin, Chlormadinone, Chlorprothixene, Cholecalciferol, Ciclopirox, Cisapride, Clomipramine, Clotrimazole, Cobimetinib, Cyproheptadine, Daunorubicin, Delavirdine, Deoxycholic Acid, Dexamethasone, Dextrothyroxine, Diethylstilbestrol, Doxazosin, Doxorubicin, Dronedarone, Duvelisib, Dydrogesterone, Enasidenib, Enoxacin