MK-0524: a potent orally active human prostaglandin D(2) receptor 1 antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 9867642 |
| CHEMBL ID | 426559 |
| CHEBI ID | 135942 |
| SCHEMBL ID | 991107 |
| MeSH ID | M0507931 |
| Synonym |
|---|
| HY-50175 |
| LAROPIPRANT,CAS:571170-77-9 |
| cardaptive; mk 0524; mk-0524 |
| laropiprant |
| CHEBI:135942 |
| cordaptive |
| mk-0524 |
| CHEMBL426559 , |
| 571170-77-9 |
| D08940 |
| laropiprant (inn/usan) |
| bdbm50205275 |
| [(3r)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid |
| mk 0524 |
| laropiprant;(r)-2-(4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid |
| A25234 |
| unii-g7n11t8o78 |
| cyclopent(b)indole-3-acetic acid, 4-((4-chlorophenyl)methyl)-7-fluoro-1,2,3,4-tetrahydro-5-(methylsulfonyl)-, (3r)- |
| (-)-((3r)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta(b)indol-3-yl)acetic acid |
| laropiprant [usan:inn:ban] |
| cardaptive |
| g7n11t8o78 , |
| tedaptive |
| BCP9000944 |
| BCPP000161 |
| laropiprant [mart.] |
| laropiprant [mi] |
| laropiprant [who-dd] |
| laropiprant [inn] |
| laropiprant [ema epar] |
| laropiprant [usan] |
| CS-0539 |
| gtpl3356 |
| mk0524 |
| 2-[(3r)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-methanesulfonyl-1h,2h,3h,4h-cyclopenta[b]indol-3-yl]acetic acid |
| AM81247 |
| cyclopent[b]indole-3-acetic acid, 4-[(4-chlorophenyl)methyl]-7-fluoro-1,2,3,4-tetrahydro-5-(methylsulfonyl)-, (3r)- |
| 2-[(3r)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid |
| SCHEMBL991107 |
| DTXSID60205756 |
| AKOS030526850 |
| NCGC00345790-10 |
| laropiprant (mk-0524) |
| laropiprant; mk-0524 |
| EX-A2099 |
| DB11629 |
| (r)-2-(4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid |
| AS-17012 |
| BCP02136 |
| Q412291 |
| ((3r)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta(b)indol-3-yl)acetic acid |
| EN300-25916161 |
| AT34794 |
| AC-35835 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Treatment-related adverse experiences (AEs) related to flushing, pruritis, rash, gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs." | ( Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Ceska, R; Giezek, H; Gil-Extremera, B; Maccubbin, D; Mao, A; McCrary Sisk, C; Paolini, JF; Shah, S; Vandormael, K, 2010) | 0.36 |
| "The safety and tolerability profile for ERN/LRPT was similar to that of ERN-NSP, except for fewer flushing-related adverse experiences and discontinuations with ERN/LRPT than ERN-NSP." | ( Safety of extended-release niacin/laropiprant in patients with dyslipidemia. Ballantyne, CM; Bays, H; Betteridge, A; Koren, M; Kuznetsova, O; Maccubbin, D; McKenney, J; Mitchel, Y; Paolini, JF; Sapre, A; Sisk, CM, ) | 0.13 |
| "The addition of LRP to ERN, by reducing the side effect 'flushing', may enable lipidologists and physicians to use niacin more widely as part of lipid modification therapy, especially since the combination can be safely added to statins." | ( Safety and tolerability of extended-release niacin with laropiprant. Ammori, BJ; Issa, B; Kwok, S; Soran, H; Yadav, R, 2012) | 0.38 |
| " Adverse experiences (AEs) typically associated with niacin (flushing, pruritus, increased glucose, increased uric acid) were more common with ERN/LRPT+SIMVA, and hepatic-related laboratory AEs were more common with ATORVA." | ( Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia. Blomqvist, P; Chen, E; Chen, F; Davidson, M; Maccubbin, D; McKenney, JM; Sirah, W; Sisk, CM; Yan, L, 2013) | 0.39 |
| " ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding)." | ( Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials. Bays, H; Gleim, G; Kuznetsova, O; Maccubbin, D; McKenney, J; Mitchel, Y; Sapre, A; Sirah, W, ) | 0.13 |
| "Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN." | ( Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials. Bays, H; Gleim, G; Kuznetsova, O; Maccubbin, D; McKenney, J; Mitchel, Y; Sapre, A; Sirah, W, ) | 0.13 |
| "Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown." | ( Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs. Armitage, J; Collins, R; Gray, A; Haynes, R; Hopewell, JC; Kent, S; Landray, MJ; Mihaylova, B; Parish, S, 2016) | 0.43 |
| " The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs." | ( Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs. Armitage, J; Collins, R; Gray, A; Haynes, R; Hopewell, JC; Kent, S; Landray, MJ; Mihaylova, B; Parish, S, 2016) | 0.43 |
| " However, the trial also identified previously unrecognized serious adverse effects (including new-onset diabetes, bleeding, and infection)." | ( Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Armitage, J; Chen, F; Haynes, R; Hopewell, JC; Landray, MJ; Li, J; Parish, S; Valdes-Marquez, E, 2019) | 0.51 |
| " The excess risks of these serious adverse events were larger in the first year after starting niacin-laropiprant therapy than in later years (except for the excess of infection, which did not appear to attenuate with time), and the risks of nonfatal and fatal events were similarly increased." | ( Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Armitage, J; Chen, F; Haynes, R; Hopewell, JC; Landray, MJ; Li, J; Parish, S; Valdes-Marquez, E, 2019) | 0.51 |
| "Practitioners or patients considering the use of niacin (in addition to, or instead of, a statin) despite the lack of evidence of cardiovascular benefits (at least when added to effective statin therapy) should take account of the significant risks of these serious adverse effects when making such decisions." | ( Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Armitage, J; Chen, F; Haynes, R; Hopewell, JC; Landray, MJ; Li, J; Parish, S; Valdes-Marquez, E, 2019) | 0.51 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " These results demonstrate that laropiprant does not enhance in vivo platelet reactivity, either alone or in combination with niacin." | ( 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. Chao, A; Cote, J; Dishy, V; Gutierrez, M; Lai, E; Larson, P; Laterza, O; Lauring, B; Luo, WL; Patterson, J; Wagner, JA, 2009) | 0.35 |
| "Understanding and documentation of drug-drug interactions (DDIs) are an important component of drug development, and of clinical therapeutics." | ( Drug-drug noninteractions. Greenblatt, DJ, 2009) | 0.35 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Absolute oral bioavailability values in rats, dogs and monkeys were 50, 70 and 8%, respectively." | ( The pharmacokinetics and disposition of MK-0524, a Prosglandin D2 Receptor 1 antagonist, in rats, dogs and monkeys. Chang, SW; Dean, BJ; Franklin, RB; Karanam, BV; Pereira, T; Reddy, V; Seto, C; Xia, YQ, 2007) | 0.61 |
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " Results from early dosing and formulation studies have culminated in the development of a combination extended-release (ER) niacin/laropiprant tablet aimed at providing the beneficial lipid-modifying effects of niacin, while reducing niacin-induced flushing." | ( Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors. Ballantyne, CM; Bays, HE; Davidson, M; Kuznetsova, O; Lai, E; Maccubbin, D; Mitchel, YB; Norquist, JM; Paolini, JF; Pasternak, R; Sisk, CM; Waters, MG, 2008) | 0.35 |
| " The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk." | ( Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Bays, HE; Betteridge, A; Elinoff, V; Elis, A; Kuznetsova, O; Maccubbin, D; Mitchel, Y; Olsson, AG; Paolini, JF; Pasternak, RC; Reyes, R; Sirah, W; Sisk, CM; Yu, Q, 2008) | 0.35 |
| " We compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of Kos Life Sciences LLC)." | ( Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. Davidson, M; Gavish, D; Koren, MJ; Maccubbin, D; Macdonell, G; Mallick, M; Mitchel, Y; Paolini, JF; Pasternak, RC; Sisk, CM, 2009) | 0.35 |
| " There is a need for further research in order to come to a clear conclusion regarding combined therapies of aspirin and laropiprant pretreatment, as well as exact dosage requirements." | ( Mechanisms of flushing due to niacin and abolition of these effects. Arora, R; Sood, A, 2009) | 0.35 |
| "This open-label study evaluated the influence of hepatic insufficiency on the pharmacokinetics of laropiprant (LRPT), a prostaglandin D(2) receptor-1 antagonist, to guide clinicians in the event of inadvertent dosing in patients with hepatic insufficiency." | ( Pharmacokinetics of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, in patients with moderate hepatic impairment. Johnson-Levonas, AO; Lai, E; Lasseter, KC; Liu, F; Luk, JA; Lunde, NM; Marbury, TC; Nirula, A; Wagner, JA; Wang, YH, 2011) | 0.37 |
| "The favorable safety and tolerability profile of ERN/LRPT for up to 1 year supports the use of LRPT to achieve improved therapeutic dosing of niacin, an agent with comprehensive lipid-modifying efficacy and shown to reduce cardiovascular risk." | ( Safety of extended-release niacin/laropiprant in patients with dyslipidemia. Ballantyne, CM; Bays, H; Betteridge, A; Koren, M; Kuznetsova, O; Maccubbin, D; McKenney, J; Mitchel, Y; Paolini, JF; Sapre, A; Sisk, CM, ) | 0.13 |
| " The favorable safety profile supports the use of LRP to achieve higher therapeutic dosing of niacin." | ( Safety and tolerability of extended-release niacin with laropiprant. Ammori, BJ; Issa, B; Kwok, S; Soran, H; Yadav, R, 2012) | 0.38 |
| "The relationship of the exanthematous eruption with lower body weight and the increase in dosage suggests a pharmacokinetic effect that may be related to increased exposure to niacin or its metabolites and provoked by inhibition of the DP1 receptor with laropiprant, as we have not seen this rash with niacin used alone." | ( A high incidence of exanthematous eruption associated with niacin/laropiprant combination in Hong Kong Chinese patients. Chang, M; Hu, M; Tomlinson, B; Yang, YL, 2013) | 0.39 |
| Class | Description |
|---|---|
| indolyl carboxylic acid | |
| [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 | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Thromboxane A2 receptor | Homo sapiens (human) | Ki | 0.5815 | 0.0006 | 1.2407 | 3.8040 | AID277845; AID277846 |
| Prostaglandin E2 receptor EP1 subtype | Homo sapiens (human) | Ki | 1.1600 | 0.0091 | 0.6635 | 1.5849 | AID277846 |
| Prostaglandin E2 receptor EP4 subtype | Homo sapiens (human) | Ki | 15.2000 | 0.0001 | 0.4744 | 3.1623 | AID277849 |
| Prostaglandin F2-alpha receptor | Homo sapiens (human) | Ki | 9.9910 | 0.0310 | 3.3803 | 9.9910 | AID277850 |
| Prostaglandin E2 receptor EP3 subtype | Homo sapiens (human) | Ki | 0.8920 | 0.0003 | 1.7081 | 6.8000 | AID277848 |
| Prostaglandin E2 receptor EP2 subtype | Homo sapiens (human) | Ki | 0.1360 | 0.0010 | 0.5448 | 3.0000 | AID277847 |
| Prostacyclin receptor | Homo sapiens (human) | Ki | 6.6280 | 0.0032 | 0.4958 | 6.6280 | AID277851 |
| Prostaglandin D2 receptor | Homo sapiens (human) | IC50 (µMol) | 0.0007 | 0.0001 | 1.1583 | 7.3000 | AID277852; AID277879 |
| Prostaglandin D2 receptor | Homo sapiens (human) | Ki | 0.0006 | 0.0006 | 0.4913 | 1.4000 | AID277844 |
| Prostaglandin D2 receptor 2 | Homo sapiens (human) | Ki | 0.7450 | 0.0006 | 0.6735 | 8.0000 | AID277874 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Thromboxane A2 receptor | Homo sapiens (human) | Kd | 0.0109 | 0.0109 | 6.1027 | 8.2000 | AID277845 |
| Prostaglandin D2 receptor | Homo sapiens (human) | Kd | 0.0000 | 0.0000 | 0.0000 | 0.0000 | AID277844 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 27 (24.55) | 29.6817 |
| 2010's | 80 (72.73) | 24.3611 |
| 2020's | 3 (2.73) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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 weak demand-to-supply ratio for research on this compound.
| This Compound (14.69) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 57 (47.11%) | 5.53% |
| Reviews | 19 (15.70%) | 6.00% |
| Case Studies | 3 (2.48%) | 4.05% |
| Observational | 1 (0.83%) | 0.25% |
| Other | 41 (33.88%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||