clazosentan: endothelin A receptor antagonist used for cerebral vasospasm; structure in first source; [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 6433095 |
| CHEMBL ID | 109648 |
| SCHEMBL ID | 1652657 |
| MeSH ID | M0499083 |
| Synonym |
|---|
| clazosentan |
| axv 034 |
| n-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-(1h-tetrazol-5-yl)pyridin-4-yl)pyrimidin-4-yl)-5-methylpyridine-2-sulfonamide |
| axv-034343 |
| axv-034 |
| axv-343434 |
| 180384-56-9 |
| ro-61-1790 |
| ro 61-1790 |
| vml-588 |
| vml 588 |
| act-108475 |
| CHEMBL109648 , |
| 5-methyl-pyridine-2-sulfonic acid {6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(2h-tetrazol-5-yl)-pyridin-4-yl]-pyrimidin-4-yl}-amide |
| bdbm50066370 |
| n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide |
| unii-3drr0x4728 |
| n-{6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-(1h-tetrazol-5-yl)pyridin-4-yl)pyrimidin-4-yl}-5-methylpyridine-2-sulfonamide |
| who 8397 |
| 3drr0x4728 , |
| axv 034343 |
| clazosentan [usan:inn] |
| clazosentan [usan] |
| clazosentan [mi] |
| clazosentan [who-dd] |
| clazosentan [inn] |
| 2-pyridinesulfonamide, n-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-(1h-tetrazol-5-yl)-4-pyridinyl)-4-pyrimidinyl)-5-methyl- |
| SCHEMBL1652657 |
| DTXSID60170955 |
| FT-0765561 |
| n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-methyl-pyridine-2-sulfonamide |
| DB06677 |
| Q1099339 |
| axv034343 |
| gtpl12286 |
| pivlaz |
| compound 22 [pmid: 9703472] |
| SB18855 |
| clazosentan (usan/inn) |
| D11664 |
| D85521 |
| n-(2-(2-(1h-tetrazol-5-yl)pyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl)-5-methylpyridine-2-sulfonamide |
| MS-30385 |
| 2-pyridinesulfonamide, n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)-4-pyridinyl]-4-pyrimidinyl]-5-methyl- |
| BC162764 |
| CS-0006250 |
| HY-17352 |
Clazosentan is a selective endothelin A receptor antagonist. It is in clinical development for the treatment of aneurysmal subarachnoid haemorrhage.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Clazosentan is a selective endothelin A receptor antagonist in development for the prevention and treatment of vasospasm postsubarachnoid hemorrhage. " | ( Influence of Rifampin-Mediated Organic Anion-Transporting Polypeptide 1B1/1B3 Inhibition on the Pharmacokinetics of Clazosentan. Dingemanse, J; Dogterom, P; Juif, PE; Ufer, M; Voors-Pette, C, 2019) | 2.17 |
| "Clazosentan is an endothelin receptor antagonist designed to prevent endothelin-mediated cerebral vasospasm." | ( Clazosentan: prevention of cerebral vasospasm and the potential to overcome infarction. Beck, J; Raabe, A, 2011) | 2.53 |
| "Clazosentan is a selective endothelin A receptor antagonist, formulated for parenteral use, which is in clinical development for the treatment of aneurysmal subarachnoid haemorrhage. " | ( Influence of different degrees of liver impairment on the pharmacokinetics of clazosentan. Bruderer, S; Detishin, V; Dingemanse, J; Tsvitbaum, N, 2011) | 2.04 |
Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosetan compared with placebo after aSAH.
Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome. Rats treated with clazosetan had less large-artery vasospsam compared to vehicle-treated controls.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome." | ( Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors. Dienel, A; Liu, H; Nehrkorn, K; Plesnila, N; Schöller, K; Schwarzmaier, SM; Terpolilli, NA, 2018) | 1.92 |
| "Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls." | ( Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats. Ai, J; Chen, G; Jeon, HJ; Lakovic, K; Macdonald, RL; Sabri, M; Tang, EJ; Tariq, A; Wan, H, 2011) | 1.01 |
Adverse events were increased by clazosentan (RR 1.5)
The elimination of clazosentan was characterized by a very rapid disposition phase with a half-life of 6-10 min. The pharmacokinetic (PK) parameters were determined by both model-independent and model-dependent methods.
The results of this study will allow confident dosing of clazosentan in individuals with moderate and severe liver impairment. The data suggest that Caucasian and Japanese patients can be treated with a similar dosing regimen.
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Endothelin receptor type B | Homo sapiens (human) | IC50 (µMol) | 0.1750 | 0.0001 | 0.6565 | 9.8000 | AID1626368 |
| Endothelin receptor type B | Homo sapiens (human) | Ki | 0.1750 | 0.0001 | 0.0543 | 0.3710 | AID66692 |
| Endothelin-1 receptor | Homo sapiens (human) | IC50 (µMol) | 0.0017 | 0.0000 | 0.7647 | 9.9000 | AID1626371 |
| Endothelin-1 receptor | Homo sapiens (human) | Ki | 0.0001 | 0.0000 | 0.4300 | 10.0000 | AID68489 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| endothelin receptor activity | Endothelin receptor type B | Homo sapiens (human) |
| protein binding | Endothelin receptor type B | Homo sapiens (human) |
| peptide hormone binding | Endothelin receptor type B | Homo sapiens (human) |
| type 1 angiotensin receptor binding | Endothelin receptor type B | Homo sapiens (human) |
| phosphatidylinositol phospholipase C activity | Endothelin-1 receptor | Homo sapiens (human) |
| endothelin receptor activity | Endothelin-1 receptor | Homo sapiens (human) |
| protein binding | Endothelin-1 receptor | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| plasma membrane | Endothelin receptor type B | Homo sapiens (human) |
| nuclear membrane | Endothelin receptor type B | Homo sapiens (human) |
| plasma membrane | Endothelin receptor type B | Homo sapiens (human) |
| plasma membrane | Endothelin-1 receptor | Homo sapiens (human) |
| plasma membrane | Endothelin-1 receptor | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1626371 | Displacement of 125I-ET1 from ETA receptor (unknown origin) expressed in CHO cells | 2016 | Bioorganic & medicinal chemistry letters, 08-01, Volume: 26, Issue:15 | From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective. |
| AID1626368 | Displacement of radioligand from ETB receptor in human placenta cell membranes | 2016 | Bioorganic & medicinal chemistry letters, 08-01, Volume: 26, Issue:15 | From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective. |
| AID419501 | Volume of distribution at steady state in human administered three sequential 4-h infusion at 1, 5 and 15 mg/hr | 2009 | Journal of medicinal chemistry, Jul-23, Volume: 52, Issue:14 | In silico prediction of volume of distribution in human using linear and nonlinear models on a 669 compound data set. |
| AID22751 | Pharmacokinetic profile-half life was evaluated in rats upon intravenous administration | 1998 | Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17 | Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546). |
| AID18623 | Pharmacokinetic profile bioavailability was evaluated in rats; Not available | 1998 | Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17 | Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546). |
| AID230232 | Inhibitory selectivity ratio for pETB / ETA | 1998 | Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17 | Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546). |
| AID66692 | Tested for binding affinity for human Endothelin B receptor by measuring its ability to displace [125I]-ET-3 from chinese hamster ovary cells(CHO) | 1998 | Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17 | Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546). |
| AID68489 | Tested for binding affinity for human Endothelin A receptor by measuring its ability to displace [125I]-ET-1 from chinese hamster ovary cells(CHO) | 1998 | Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17 | Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546). |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 6 (6.52) | 18.2507 |
| 2000's | 22 (23.91) | 29.6817 |
| 2010's | 51 (55.43) | 24.3611 |
| 2020's | 13 (14.13) | 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 strong demand-to-supply ratio for research on this compound.
| This Compound (39.87) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 33 (35.11%) | 5.53% |
| Reviews | 16 (17.02%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 1 (1.06%) | 0.25% |
| Other | 44 (46.81%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||