PALOSURAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H30N4O2
Molecular Weight	418.5313
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(NC(=O)NCCN2CCC(O)(CC3=CC=CC=C3)CC2)=C4C=CC=CC4=N1

InChI

InChIKey=WYJCYXOCHXWTHG-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15146030 | https://www.ncbi.nlm.nih.gov/pubmed/23904152
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800014355

Palosuran, also known as ACT-058362, a potent and specific antagonist of the human UT receptor. Urotensin inhibition with palosuran was 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. Phase-II clinical trials for diabetic nephropathies and cardiovascular disorders were discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Urotensin II receptor 2 Target ID: CHEMBL3764 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15146030 \| https://www.ncbi.nlm.nih.gov/pubmed/21561377	Antagonist 2849		3.6 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetic nephropathy 37 Sources: http://adisinsight.springer.com/drugs/800014355 https://www.ncbi.nlm.nih.gov/pubmed/20231521 https://www.ncbi.nlm.nih.gov/pubmed/19843053	Primary		Phase II 1147	Unknown Approved Use Unknown
Cardiovascular diseases 72 Sources: http://adisinsight.springer.com/drugs/800014355 https://www.ncbi.nlm.nih.gov/pubmed/17900760	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
135 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16952491/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
107 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16952491/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
196 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
431 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1069 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1615 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
433 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16952491/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
429 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16952491/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
735 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
34.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1429 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
84.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3350 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9216 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
29.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	125 mg 2 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
23.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30384375/	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PALOSURAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2000 mg single, oral Highest studied dose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	Other AEs: vomiting, diarrhea... Other AEs: vomiting (2 patients) diarrhea (1 pt) Fatigue (2 patients) Fatigue (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19625629
500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	Other AEs: Abdominal distension, diarrhea... Other AEs: Abdominal distension (1 pt) diarrhea (2 patients) fatigue (1 pt) loose stools (1 pt) Abdominal pain upper (1 pt) Dyspepsia (1 pt) headache (1 pt) Nausea (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/30384375

AEs

AE	Significance	Dose	Population
Fatigue	1 pt	2000 mg single, oral Highest studied dose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19625629
diarrhea	1 pt	2000 mg single, oral Highest studied dose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19625629
Fatigue	2 patients	2000 mg single, oral Highest studied dose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19625629
vomiting	2 patients	2000 mg single, oral Highest studied dose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19625629	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19625629
Abdominal distension	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
Abdominal pain upper	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
Dyspepsia	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
Nausea	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
fatigue	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
headache	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
loose stools	1 pt	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375
diarrhea	2 patients	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30384375	healthy Health Status: healthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30384375

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY442977	https://www.001chemical.com/chem/search?q=DY442977
1PlusChem LLC	1P00DBNT	https://www.1pchem.com/search?query=1P00DBNT
Aceschem	ACS019820	https://www.aceschem.com/catalog/search.do?q=ACS019820
AChemBlock	O33756	http://www.achemblock.com/catalogsearch/result/?q=O33756
AOBIOUS INC	AOB87328	http://aobious.com/aobious/search?search_query=AOB87328
ApexBio Technology	B1304	https://www.apexbt.com/catalogsearch/result/?q=B1304
BLD Pharm	BD448329	http://www.bldpharm.com/search/Search.html?keyword=BD448329
BOC Sciences	540769-28-6	http://www.bocsci.com/description.asp?cas=540769-28-6
Capot Chemical	33948	https://www.capotchem.com/search.do?q=33948
Chem Scene	CS-1722	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1722
ChemShuttle	153165	https://www.chemshuttle.com/catalogsearch/result/?q=153165
Combi-Blocks	QJ-6302	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-6302
eMolecules	50285382	https://orderbb.emolecules.com/search/#?query=50285382
eNovation Chemicals	D509233	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D509233&searchbtn.x=0&searchbtn.y=0
Hairui	HR32973	http://www.hairuichem.com/en/product/search.do?q=HR32973
Lab Seeker	SC-87805	http://www.labseeker.com/search.php?keywords=SC-87805&category=0
LabSeeker	SC-87805	http://www.labseeker.com/search.php?keywords=SC-87805&category=0
mcule	MCULE-2793125137	https://mcule.com/MCULE-2793125137/
MedChem Express	HY-10655	https://www.medchemexpress.com/search.html?q=HY-10655&ft=&fa=&fp=
Molcore	MC442977	http://www.molcore.com/CatMC442977.html
Molnova	M14932	https://www.molnova.com/en/serch-list.html?keywords=M14932
Molnova	M17710	https://www.molnova.com/en/serch-list.html?keywords=M17710
MolPort	MolPort-039-331-992	https://www.molport.com/shop/molecule-link/MolPort-039-331-992
MuseChem	I003982	https://www.musechem.com/product/I003982.html
ShangHai Biochempartner	BCP15786	http://www.biochempartner.com/search_BCP15786
TargetMol	T2058	https://www.targetmol.com/search?keyword=T2058
TargetMol	T4689	https://www.targetmol.com/search?keyword=T4689

PubMed

Title	Date	PubMed
Urotensin II receptor and acetylcholine release from mouse cervical spinal cord nerve terminals.	2010-09-29	20620192
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.	2010-09-03	20683923
Late-onset circulatory dysfunction after thyroid hormone treatment in an extremely low birth weight infant.	2010-05-04	20432818
Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy.	2010-05	20231521
Expression of urotensin II and its receptor in human liver cirrhosis and fulminant hepatic failure.	2010-05	19582578
Urotensin-II contributes to pulmonary vasoconstriction in a perinatal model of persistent pulmonary hypertension of the newborn secondary to meconium aspiration syndrome.	2010-02	19809374
Pro-angiogenic activity of Urotensin-II on different human vascular endothelial cell populations.	2009-10-09	19362580
Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus.	2009-10	19843053
Pharmacokinetics and pharmacodynamics of the urotensin-II receptor antagonist palosuran in healthy male subjects.	2009-10	19625629
Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel insights for the pathophysiology of primary aldosteronism.	2009-02	19001524
Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues.	2008-10	18587423
Urotensin II and urotensin II-related peptide activate somatostatin receptor subtypes 2 and 5.	2008-05	18289730
Cardiorenovascular effects of urotensin II and the relevance of the UT receptor.	2008-05	17935830
Evidence for endogenous urotensin-II as an inhibitor of insulin secretion. Study in the perfused rat pancreas.	2008-05	17931748
Urotensin II and urotensin II-related peptide (URP) in cardiac ischemia-reperfusion injury.	2008-05	17900760
Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus.	2008-04-23	18463714
Urotensin II: a new pharmacologic target in the treatment of cardiovascular disease.	2008-04-17	18414185
Non peptidic urotensin II antagonists: perspectives for a new class of drugs.	2008-04	18473773
Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats.	2008-04	18318439
Urotensin II in cardiovascular regulation.	2008	19065995
Role of urotensin II and its receptor in health and disease.	2007	17680191
Urotensin-II and its receptor (UT-R) are expressed in rat brain endothelial cells, and urotensin-II via UT-R stimulates angiogenesis in vivo and in vitro.	2006-12	17089015
Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients.	2006-09	16952491
Urotensin-II and UII-receptor expression and function in the rat adrenal cortex.	2006-06	16685423
The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats.	2006-03	16267137
Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats.	2005-03	15710491
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.	2004-10	15146030

Patents

Sample Use Guides

In Vivo Use Guide

Patients with 24-hour albuminuria >0.5 and <3.0 g, systolic blood pressure >135 and <170 mm Hg, and/or diastolic blood pressure >85 and <110 mm Hg received both palosuran 125 mg BID and placebo for 4 weeks each

Route of Administration: Oral

In Vitro Use Guide

1 uM palosuran significantly decreased Urotensin-II induced contraction of rat aortic rings

Name

Type

Language

PALOSURAN

Official Name

English

ACT-058362

Preferred Name

English

palosuran [INN]

Common Name

English

1-(2-(4-BENZYL-4-HYDROXYPIPERIDIN-1-YL)ETHYL)-3-(2-METHYLQUINOLIN-4-YL)UREA

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29707