Palosuran
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MedKoo CAT#: 329464

CAS#: 540769-28-6

Description: Palosuran, also known as ACT-058362, is a Urotensin-II receptor antagonist. Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertension. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Palosuran improves pancreatic and renal function in diabetic rats.


Chemical Structure

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Palosuran
CAS# 540769-28-6

Theoretical Analysis

MedKoo Cat#: 329464
Name: Palosuran
CAS#: 540769-28-6
Chemical Formula: C25H30N4O2
Exact Mass: 418.24
Molecular Weight: 418.541
Elemental Analysis: C, 71.74; H, 7.23; N, 13.39; O, 7.65

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to Ship
10mg USD 165 Ready to Ship
25mg USD 350 Ready to Ship
50mg USD 550 Ready to Ship
100mg USD 950 Ready to Ship
200mg USD 1650 Ready to Ship
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Related CAS #: 540769-28-6    

Synonym: Palosuran; ACT-058362; ACT058362; ACT 058362.

IUPAC/Chemical Name: 1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea

InChi Key: WYJCYXOCHXWTHG-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H30N4O2/c1-19-17-23(21-9-5-6-10-22(21)27-19)28-24(30)26-13-16-29-14-11-25(31,12-15-29)18-20-7-3-2-4-8-20/h2-10,17,31H,11-16,18H2,1H3,(H2,26,27,28,30)

SMILES Code: O=C(NC1=CC(C)=NC2=CC=CC=C12)NCCN3CCC(CC4=CC=CC=C4)(O)CC3

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

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

More Info:

Biological target: Palosuran (ACT-058362) is a potent, selective, and orally active antagonist of urotensin II receptor, with an IC50 of 3.6 nM for CHO cell membranes expressing human recombinant receptors.
In vitro activity: ACT-058362 antagonizes the specific binding of (125)I-labeled U-II on natural and recombinant cells carrying the human UT receptor with a high affinity in the low nanomolar range and a competitive mode of antagonism, revealed only with prolonged incubation times. ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. Reference: J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. https://pubmed.ncbi.nlm.nih.gov/15146030/
In vivo activity: Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage. Reference: J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21. https://pubmed.ncbi.nlm.nih.gov/16267137/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 10.0 23.89
DMO 30.0 71.68
DMSO:PBS (pH 7.2) (1:1) 0.5 1.19
Ethanol 0.5 1.19

Preparing Stock Solutions

The following data is based on the product molecular weight 418.54 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.

Recalculate based on batch purity %
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
Formulation protocol: 1. Clozel M, Binkert C, Birker-Robaczewska M, Boukhadra C, Ding SS, Fischli W, Hess P, Mathys B, Morrison K, Müller C, Müller C, Nayler O, Qiu C, Rey M, Scherz MW, Velker J, Weller T, Xi JF, Ziltener P. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. doi: 10.1124/jpet.104.068320. Epub 2004 May 14. PMID: 15146030. 2. Behm DJ, McAtee JJ, Dodson JW, Neeb MJ, Fries HE, Evans CA, Hernandez RR, Hoffman KD, Harrison SM, Lai JM, Wu C, Aiyar NV, Ohlstein EH, Douglas SA. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br J Pharmacol. 2008 Oct;155(3):374-86. doi: 10.1038/bjp.2008.266. Epub 2008 Jun 30. PMID: 18587423; PMCID: PMC2567886. 3. Yin L, Li N, Jia W, Wang N, Liang M, Shang J, Qiang G, Du G, Yang X. Urotensin receptor acts as a novel target for ameliorating fasting-induced skeletal muscle atrophy. Pharmacol Res. 2022 Nov;185:106468. doi: 10.1016/j.phrs.2022.106468. Epub 2022 Sep 24. PMID: 36167277. 4. Clozel M, Hess P, Qiu C, Ding SS, Rey M. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21. doi: 10.1124/jpet.105.094821. Epub 2005 Nov 2. PMID: 16267137.
In vitro protocol: 1. Clozel M, Binkert C, Birker-Robaczewska M, Boukhadra C, Ding SS, Fischli W, Hess P, Mathys B, Morrison K, Müller C, Müller C, Nayler O, Qiu C, Rey M, Scherz MW, Velker J, Weller T, Xi JF, Ziltener P. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. doi: 10.1124/jpet.104.068320. Epub 2004 May 14. PMID: 15146030. 2. Behm DJ, McAtee JJ, Dodson JW, Neeb MJ, Fries HE, Evans CA, Hernandez RR, Hoffman KD, Harrison SM, Lai JM, Wu C, Aiyar NV, Ohlstein EH, Douglas SA. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br J Pharmacol. 2008 Oct;155(3):374-86. doi: 10.1038/bjp.2008.266. Epub 2008 Jun 30. PMID: 18587423; PMCID: PMC2567886.
In vivo protocol: 1. Yin L, Li N, Jia W, Wang N, Liang M, Shang J, Qiang G, Du G, Yang X. Urotensin receptor acts as a novel target for ameliorating fasting-induced skeletal muscle atrophy. Pharmacol Res. 2022 Nov;185:106468. doi: 10.1016/j.phrs.2022.106468. Epub 2022 Sep 24. PMID: 36167277. 2. Clozel M, Hess P, Qiu C, Ding SS, Rey M. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21. doi: 10.1124/jpet.105.094821. Epub 2005 Nov 2. PMID: 16267137.

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1: Pehlivan Y, Dokuyucu R, Demir T, Kaplan DS, Koc I, Orkmez M, Turkbeyler IH, Ceribasi AO, Tutar E, Taysi S, Kisacik B, Onat AM. Palosuran treatment effective as bosentan in the treatment model of pulmonary arterial hypertension. Inflammation. 2014 Aug;37(4):1280-8. doi: 10.1007/s10753-014-9855-8. PubMed PMID: 24604341.

2: Onat AM, Pehlivan Y, Turkbeyler IH, Demir T, Kaplan DS, Ceribasi AO, Orkmez M, Tutar E, Taysi S, Sayarlioglu M, Kisacik B. Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertension. Inflammation. 2013 Apr;36(2):405-12. doi: 10.1007/s10753-012-9559-x. PubMed PMID: 23100033.

3: Demir T, Turkbeyler I, Kaplan DS, Pehlivan Y, Orkmez M, Tutar E, Taysi S, Kisacik B, Onat AM, Bagcı C. Effectiveness of palosuran in bleomycin-induced experimental scleroderma. Inflammation. 2013 Feb;36(1):75-9. doi: 10.1007/s10753-012-9521-y. PubMed PMID: 22886350.

4: Vogt L, Chiurchiu C, Chadha-Boreham H, Danaietash P, Dingemanse J, Hadjadj S, Krum H, Navis G, Neuhart E, Parvanova AI, Ruggenenti P, Woittiez AJ, Zimlichman R, Remuzzi G, de Zeeuw D; PROLONG (PROteinuria Lowering with urOteNsin receptor antaGonists) Study Group.. Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy. Hypertension. 2010 May;55(5):1206-9. doi: 10.1161/HYPERTENSIONAHA.109.149559. PubMed PMID: 20231521.

5: Sidharta PN, Rave K, Heinemann L, Chiossi E, Krähenbühl S, Dingemanse J. Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus. Br J Clin Pharmacol. 2009 Oct;68(4):502-10. doi: 10.1111/j.1365-2125.2009.03480.x. PubMed PMID: 19843053; PubMed Central PMCID: PMC2780275.

6: Sidharta PN, van Giersbergen PL, Dingemanse J. Pharmacokinetics and pharmacodynamics of the urotensin-II receptor antagonist palosuran in healthy male subjects. J Clin Pharmacol. 2009 Oct;49(10):1168-75. doi: 10.1177/0091270009341181. PubMed PMID: 19625629.

7: Behm DJ, McAtee JJ, Dodson JW, Neeb MJ, Fries HE, Evans CA, Hernandez RR, Hoffman KD, Harrison SM, Lai JM, Wu C, Aiyar NV, Ohlstein EH, Douglas SA. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br J Pharmacol. 2008 Oct;155(3):374-86. doi: 10.1038/bjp.2008.266. PubMed PMID: 18587423; PubMed Central PMCID: PMC2567886.

8: Trebicka J, Leifeld L, Hennenberg M, Biecker E, Eckhardt A, Fischer N, Pröbsting AS, Clemens C, Lammert F, Sauerbruch T, Heller J. Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats. Hepatology. 2008 Apr;47(4):1264-76. doi: 10.1002/hep.22170. PubMed PMID: 18318439.

9: Sidharta PN, Wagner FD, Bohnemeier H, Jungnik A, Halabi A, Krähenbühl S, Chadha-Boreham H, Dingemanse J. Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients. Clin Pharmacol Ther. 2006 Sep;80(3):246-56. PubMed PMID: 16952491.

10: Clozel M, Hess P, Qiu C, Ding SS, Rey M. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21. PubMed PMID: 16267137.

11: Clozel M, Binkert C, Birker-Robaczewska M, Boukhadra C, Ding SS, Fischli W, Hess P, Mathys B, Morrison K, Müller C, Müller C, Nayler O, Qiu C, Rey M, Scherz MW, Velker J, Weller T, Xi JF, Ziltener P. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. PubMed PMID: 15146030.