Palosuran | ACT-058362 | CAS#540769-28-6 | Urotensin-II receptor antagonist

MedKoo Cat#: 329464 | Name: Palosuran

Description:

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

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

Palosuran

CAS#540769-28-6

Theoretical Analysis

MedKoo Cat#: 329464

Name: Palosuran

CAS#: 540769-28-6

Chemical Formula: C25H30N4O2

Exact Mass: 418.2369

Molecular Weight: 418.54

Elemental Analysis: C, 71.74; H, 7.23; N, 13.39; O, 7.65

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to Ship
10mg	USD 250.00	Ready to Ship
50mg	USD 475.00	Ready to Ship
25mg	USD 530.00	Ready to Ship
100mg	USD 805.00	Ready to Ship
200mg	USD 1,365.00	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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A23T03K28

QC Data

View QC data: current batch, Lot#A23T03K28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Halici Z, Bulut V, Cadirci E, Yayla M. Investigation of the effects of urotensin II receptors in LPS-induced inflammatory response in HUVEC cell line through calcineurin/NFATc/IL-2 pathway. Adv Med Sci. 2023 Sep;68(2):433-440. doi: 10.1016/j.advms.2023.10.008. Epub 2023 Oct 30. PMID: 37913738. 2: 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. 3: Khurana N, James S, Coughlan MT, MacIsaac RJ, Ekinci EI. Novel Therapies for Kidney Disease in People With Diabetes. J Clin Endocrinol Metab. 2022 Jan 1;107(1):e1-e24. doi: 10.1210/clinem/dgab639. PMID: 34460928. 4: Le Joncour V, Guichet PO, Dembélé KP, Mutel A, Campisi D, Perzo N, Desrues L, Modzelewski R, Couraud PO, Honnorat J, Ferracci FX, Marguet F, Laquerrière A, Vera P, Bohn P, Langlois O, Morin F, Gandolfo P, Castel H. Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma. Front Cell Dev Biol. 2021 Apr 14;9:652544. doi: 10.3389/fcell.2021.652544. PMID: 33937253; PMCID: PMC8079989. 5: Olukman M, Can C, Coşkunsever D, Uyanikgil Y, Çavuşoğlu T, Sözmen E, Duman S, Çelenk FG, Ülker S. Urotensin receptor antagonist palosuran attenuates cyclosporine-a-induced nephrotoxicity in rats. Adv Clin Exp Med. 2019 Oct;28(10):1393-1401. doi: 10.17219/acem/104544. PMID: 31518496. 6: Zhang R, Chen J, Liu D, Wang Y. Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl4-induced cirrhotic rats. Front Med. 2019 Jun;13(3):398-408. doi: 10.1007/s11684-019-0689-5. Epub 2019 Jun 11. PMID: 30820806. 7: Sidharta PN, van Giersbergen PLM, Dingemanse J. Multiple-Dose Pharmacokinetics, Pharmacodynamics, and Safety of the Urotensin-II Receptor Antagonist Palosuran in Healthy Male Subjects. Pharmacology. 2018;102(5-6):339-346. doi: 10.1159/000492936. Epub 2018 Nov 1. PMID: 30384375. 8: Cadirci E, Ugan RA, Dincer B, Gundogdu B, Cinar I, Akpinar E, Halici Z. Urotensin receptors as a new target for CLP induced septic lung injury in mice. Naunyn Schmiedebergs Arch Pharmacol. 2019 Feb;392(2):135-145. doi: 10.1007/s00210-018-1571-8. Epub 2018 Oct 24. PMID: 30353214. 9: Ugan RA, Cadirci E, Halici Z, Toktay E, Cinar I. The role of urotensin-II and its receptors in sepsis-induced lung injury under diabetic conditions. Eur J Pharmacol. 2018 Jan 5;818:457-469. doi: 10.1016/j.ejphar.2017.11.011. Epub 2017 Nov 10. PMID: 29133126. 10: Kim SK, Goddard WA 3rd, Yi KY, Lee BH, Lim CJ, Trzaskowski B. Predicted ligands for the human urotensin-II G protein-coupled receptor with some experimental validation. ChemMedChem. 2014 Aug;9(8):1732-43. doi: 10.1002/cmdc.201402087. Epub 2014 Jul 2. PMID: 24989481. 11: 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. PMID: 24604341. 12: Hong Y, Dingemanse J, Sidharta P, Mager DE. Population pharmacodynamic modeling of hyperglycemic clamp and meal tolerance tests in patients with type 2 diabetes mellitus. AAPS J. 2013 Oct;15(4):1051-63. doi: 10.1208/s12248-013-9512-4. Epub 2013 Aug 1. PMID: 23904152; PMCID: PMC3787242. 13: 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. PMID: 23100033. 14: 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. PMID: 22886350. 15: Türkbeyler I, Demir T, Pehlivan Y, Kaplan DS, Ceribasi AO, Orkmez M, Aksoy N, Taysi S, Kisacik B, Onat AM. Prolidase could act as a diagnosis and treatment mediator in lung fibrosis. Inflammation. 2012 Oct;35(5):1747-52. doi: 10.1007/s10753-012-9493-y. PMID: 22717888. 16: Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012 Jun;97(6):2039-49. doi: 10.1210/jc.2011-3350. Epub 2012 Mar 30. PMID: 22466348. 17: Onat AM, Turkbeyler IH, Pehlivan Y, Demir T, Kaplan DS, Taysi S, Ceribasi AO, Tutar E, Kisacik B. The efficiency of a urotensin II antagonist in an experimental lung fibrosis model. Inflammation. 2012 Jun;35(3):1138-43. doi: 10.1007/s10753-011-9421-6. PMID: 22205238. 18: Tsoukas P, Kane E, Giaid A. Potential Clinical Implications of the Urotensin II Receptor Antagonists. Front Pharmacol. 2011 Jul 22;2:38. doi: 10.3389/fphar.2011.00038. PMID: 21811463; PMCID: PMC3143724. 19: Oh KS, Lee S, Lee BH. Development of filtration-based time-resolved fluorescence assay for the high-throughput screening of urotensin II receptor antagonist. Assay Drug Dev Technol. 2011 Oct;9(5):514-21. doi: 10.1089/adt.2010.0353. Epub 2011 May 11. PMID: 21561377. 20: Kim SK, Li Y, Park C, Abrol R, Goddard WA 3rd. Prediction of the three- dimensional structure for the rat urotensin II receptor, and comparison of the antagonist binding sites and binding selectivity between human and rat receptors from atomistic simulations. ChemMedChem. 2010 Sep 3;5(9):1594-608. doi: 10.1002/cmdc.201000175. PMID: 20683923; PMCID: PMC3517062.