Clazosentan

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 317104

CAS#: 180384-56-9

Description: Clazosentan, also known as Ro 61-1790, VML-588 and AXV-034, is a novel and potent endothelin A antagonist, improves cerebral blood flow and behavior after traumatic brain injury. Clazosentan is under study in clinical trials for the treatment of patients with aneurysmal subarachnoid hemorrhage (SAH) by Actelion Pharmaceuticals.Clazosentant decreases and reverses cerebral vasospasm after experimental SAH. Clazosentanthas been shown to reduce vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).


Chemical Structure

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Clazosentan
CAS# 180384-56-9

Theoretical Analysis

MedKoo Cat#: 317104
Name: Clazosentan
CAS#: 180384-56-9
Chemical Formula: C25H23N9O6S
Exact Mass: 577.1492
Molecular Weight: 577.58
Elemental Analysis: C, 51.99; H, 4.01; N, 21.83; O, 16.62; S, 5.55

Size Price Shipping out time Quantity
Inquire bulk and customized quantity

Pricing updated 2021-03-03. Prices are subject to change without notice.

Clazosentan, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Synonym: AXV034; AXV-034; AXV 034; AXV 034343; AXV-034343; AXV-343434; Ro 61-1790; Ro-61-1790; VML 588; VML-588; VML 588; Clazosentan

IUPAC/Chemical Name: N-(2-(2-(1H-tetrazol-5-yl)pyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl)-5-methylpyridine-2-sulfonamide

InChi Key: LFWCJABOXHSRGC-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H23N9O6S/c1-15-7-8-20(27-14-15)41(36,37)32-24-21(40-19-6-4-3-5-18(19)38-2)25(39-12-11-35)29-22(28-24)16-9-10-26-17(13-16)23-30-33-34-31-23/h3-10,13-14,35H,11-12H2,1-2H3,(H,28,29,32)(H,30,31,33,34)

SMILES Code: O=S(C1=NC=C(C)C=C1)(NC2=NC(C3=CC(C4=NN=NN4)=NC=C3)=NC(OCCO)=C2OC5=CC=CC=C5OC)=O

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:
2934.99.9001

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 577.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Povlsen GK, Edvinsson L. MEK1/2 inhibitor U0126 but not endothelin receptor antagonist clazosentan reduces upregulation of cerebrovascular contractile receptors and delayed cerebral ischemia, and improves outcome after subarachnoid hemorrhage in rats. J Cereb Blood Flow Metab. 2015 Feb;35(2):329-37. doi: 10.1038/jcbfm.2014.205. Epub 2014 Nov 19. PubMed PMID: 25407271; PubMed Central PMCID: PMC4426751.

2: Zisowsky J, Fuseau E, Bruderer S, Krause A, Dingemanse J. Challenges in collecting pharmacokinetic and pharmacodynamic information in an intensive care setting: PK/PD modelling of clazosentan in patients with aneurysmal subarachnoid haemorrhage. Eur J Clin Pharmacol. 2014 Apr;70(4):409-19. doi: 10.1007/s00228-014-1647-4. Epub 2014 Jan 24. PubMed PMID: 24458541.

3: Shen J, Pan JW, Fan ZX, Xiong XX, Zhan RY. Dissociation of vasospasm-related morbidity and outcomes in patients with aneurysmal subarachnoid hemorrhage treated with clazosentan: a meta-analysis of randomized controlled trials. J Neurosurg. 2013 Jul;119(1):180-9. doi: 10.3171/2013.3.JNS121436. Epub 2013 May 3. Review. PubMed PMID: 23641823.

4: Wang X, Li YM, Li WQ, Huang CG, Lu YC, Hou LJ. Effect of clazosentan in patients with aneurysmal subarachnoid hemorrhage: a meta-analysis of randomized controlled trials. PLoS One. 2012;7(10):e47778. doi: 10.1371/journal.pone.0047778. Epub 2012 Oct 17. PubMed PMID: 23082215; PubMed Central PMCID: PMC3474756.

5: Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2). Acta Neurochir Suppl. 2013;115:27-31. doi: 10.1007/978-3-7091-1192-5_7. PubMed PMID: 22890639.

6: Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Nowbakht P, Roux S, Kassell N. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012 Jun;43(6):1463-9. doi: 10.1161/STROKEAHA.111.648980. Epub 2012 Mar 8. Erratum in: Stroke. 2012 Jul;43(7):e68. PubMed PMID: 22403047.

7: Pisapia JM, Xu X, Kelly J, Yeung J, Carrion G, Tong H, Meghan S, El-Falaky OM, Grady MS, Smith DH, Zaitsev S, Muzykantov VR, Stiefel MF, Stein SC. Microthrombosis after experimental subarachnoid hemorrhage: time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan. Exp Neurol. 2012 Jan;233(1):357-63. doi: 10.1016/j.expneurol.2011.10.029. Epub 2011 Nov 4. PubMed PMID: 22079156.

8: Meyers PM, Connolly ES Jr. Stroke: disappointing results for clazosentan in CONSCIOUS-2. Nat Rev Neurol. 2011 Oct 18;7(12):660-1. doi: 10.1038/nrneurol.2011.168. PubMed PMID: 22009282.

9: Wong GK, Poon WS. Clazosentan for patients with subarachnoid haemorrhage: lessons learned. Lancet Neurol. 2011 Oct;10(10):871; author reply 871-2. doi: 10.1016/S1474-4422(11)70189-2. PubMed PMID: 21939894.

10: Kreipke CW, Rafols JA, Reynolds CA, Schafer S, Marinica A, Bedford C, Fronczak M, Kuhn D, Armstead WM. Clazosentan, a novel endothelin A antagonist, improves cerebral blood flow and behavior after traumatic brain injury. Neurol Res. 2011 Mar;33(2):208-13. doi: 10.1179/016164111X12881719352570. PubMed PMID: 21801597.

11: Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011 Jul;10(7):618-25. doi: 10.1016/S1474-4422(11)70108-9. Epub 2011 Jun 2. PubMed PMID: 21640651.

12: Ruane-O'Hora T, Rae MG, Markos F. Effect of clazosentan, a selective endothelin A receptor antagonist, and tezosentan, a dual endothelin A/B antagonist, on pulsatile shear stress induced constriction of the iliac in the anaesthetized pig. Clin Exp Pharmacol Physiol. 2011 Aug;38(8):515-20. doi: 10.1111/j.1440-1681.2011.05540.x. PubMed PMID: 21575033.

13: Chen G, Tariq A, Ai J, Sabri M, Jeon HJ, Tang EJ, Lakovic K, Wan H, Macdonald RL. Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats. Brain Res. 2011 May 25;1392:132-9. doi: 10.1016/j.brainres.2011.03.068. Epub 2011 Apr 3. PubMed PMID: 21466789.

14: Sabri M, Ai J, Macdonald RL. Dissociation of vasospasm and secondary effects of experimental subarachnoid hemorrhage by clazosentan. Stroke. 2011 May;42(5):1454-60. doi: 10.1161/STROKEAHA.110.604728. Epub 2011 Mar 31. PubMed PMID: 21454820.

15: Bruderer S, Detishin V, Tsvitbaum N, Dingemanse J. Influence of different degrees of liver impairment on the pharmacokinetics of clazosentan. Br J Clin Pharmacol. 2011 Jan;71(1):52-60. doi: 10.1111/j.1365-2125.2010.03804.x. PubMed PMID: 21143501; PubMed Central PMCID: PMC3018026.

16: Beck J, Raabe A. Clazosentan: prevention of cerebral vasospasm and the potential to overcome infarction. Acta Neurochir Suppl. 2011;110(Pt 2):147-50. doi: 10.1007/978-3-7091-0356-2_26. PubMed PMID: 21125461.

17: Bruderer S, Sasu B, Tsvitbaum N, Dingemanse J. Influence of severe renal impairment on the pharmacokinetics of clazosentan. J Clin Pharmacol. 2011 Mar;51(3):413-21. doi: 10.1177/0091270010368975. Epub 2010 Oct 6. PubMed PMID: 20926750.

18: van Giersbergen PL, Treiber A, Dingemanse J. In vitro and in vivo pharmacokinetic characteristics of clazosentan, an intravenous endothelin receptor antagonist, in humans. Int J Clin Pharmacol Ther. 2009 Mar;47(3):169-77. PubMed PMID: 19281726.

19: Schubert GA, Schilling L, Thomé C. Clazosentan, an endothelin receptor antagonist, prevents early hypoperfusion during the acute phase of massive experimental subarachnoid hemorrhage: a laser Doppler flowmetry study in rats. J Neurosurg. 2008 Dec;109(6):1134-40. doi: 10.3171/JNS.2008.109.12.1134. PubMed PMID: 19035733.

20: Macdonald RL. Clazosentan: an endothelin receptor antagonist for treatment of vasospasm after subarachnoid hemorrhage. Expert Opin Investig Drugs. 2008 Nov;17(11):1761-7. doi: 10.1517/13543784.17.11.1761 . PubMed PMID: 18922111.

Clazosentan

10mg / Not available