U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of PALOSURAN

SMILES

CC1=NC2=C(C=CC=C2)C(NC(=O)NCCN3CCC(O)(CC4=CC=CC=C4)CC3)=C1

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
Molecular Formula C25H30N4O2
Molecular Weight 418.5313
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 3.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
431 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
1069 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
11.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
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
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
196 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
21.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
1615 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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

AUC

ValueDoseCo-administeredAnalytePopulation
1429 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
3350 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
34.2 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
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
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
735 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
84.1 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
9216 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
29.9 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19625629/
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/19625629/
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/19625629/
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

Doses

DosePopulationAdverse events​
2000 mg single, oral (unknown)
Highest studied dose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
Other AEs: diarrhea, Fatigue...
Other AEs:
diarrhea (1 pt)
Fatigue (1 pt)
Fatigue (2 patients)
vomiting (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
Other AEs: Dyspepsia, headache...
Other AEs:
Dyspepsia (1 pt)
headache (1 pt)
Nausea (1 pt)
Abdominal distension (1 pt)
diarrhea (2 patients)
fatigue (1 pt)
loose stools (1 pt)
Abdominal pain upper (1 pt)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
AEs

AEs

AESignificanceDosePopulation
Fatigue 1 pt
2000 mg single, oral (unknown)
Highest studied dose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
diarrhea 1 pt
2000 mg single, oral (unknown)
Highest studied dose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
Fatigue 2 patients
2000 mg single, oral (unknown)
Highest studied dose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
vomiting 2 patients
2000 mg single, oral (unknown)
Highest studied dose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19625629
Abdominal distension 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
Abdominal pain upper 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
Dyspepsia 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
Nausea 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
fatigue 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
headache 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
loose stools 1 pt
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
diarrhea 2 patients
500 mg 2 times / day multiple, oral (unknown)
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
n = 6
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30384375
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY442977
https://www.001chemical.com/chem/search?q=DY442977
1PlusChem LLC
1P00DBNT
https://www.1pchem.com/search?query=1P00DBNT
AChemBlock
O33756
http://www.achemblock.com/catalogsearch/result/?q=O33756
AOBIOUS INC
AOB87328
http://aobious.com/aobious/search?search_query=AOB87328
Aceschem
ACS019820
https://www.aceschem.com/catalog/search.do?q=ACS019820
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
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
MedChem Express
HY-10655
https://www.medchemexpress.com/search.html?q=HY-10655&ft=&fa=&fp=
MolPort
MolPort-039-331-992
https://www.molport.com/shop/molecule-link/MolPort-039-331-992
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
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
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
mcule
MCULE-2793125137
https://mcule.com/MCULE-2793125137/
PubMed

PubMed

TitleDatePubMed
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 Oct
Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats.
2005 Mar
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 Dec
Urotensin-II and UII-receptor expression and function in the rat adrenal cortex.
2006 Jun
The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats.
2006 Mar
Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients.
2006 Sep
Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus.
2008 Apr 23
Evidence for endogenous urotensin-II as an inhibitor of insulin secretion. Study in the perfused rat pancreas.
2008 May
Urotensin II and urotensin II-related peptide (URP) in cardiac ischemia-reperfusion injury.
2008 May
Pharmacokinetics and pharmacodynamics of the urotensin-II receptor antagonist palosuran in healthy male subjects.
2009 Oct
Late-onset circulatory dysfunction after thyroid hormone treatment in an extremely low birth weight infant.
2010 Jan-Feb
Urotensin II receptor and acetylcholine release from mouse cervical spinal cord nerve terminals.
2010 Sep 29
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 Sep 3
Patents

Patents

07375227
7
08067601
1
20050043535
2
JP2006111531A
1

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
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:52:31 GMT 2023
Edited
by admin
on Sat Dec 16 15:52:31 GMT 2023
Record UNII
ULD9ZKE457
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALOSURAN
INN  
INN  
Official 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
ACT-058362
Code English
Classification Tree Code System Code
NCI_THESAURUS C29707
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
Code System Code Type Description
SMS_ID
300000036961
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
NCI_THESAURUS
C66298
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID00202406
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
ChEMBL
CHEMBL567303
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
CAS
540769-28-6
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
INN
8425
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
FDA UNII
ULD9ZKE457
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
PUBCHEM
10173280
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
MESH
C493249
Created by admin on Sat Dec 16 15:52:31 GMT 2023 , Edited by admin on Sat Dec 16 15:52:31 GMT 2023
PRIMARY
Related Record Type Details
Structure of PALOSURAN
ACTIVE MOIETY
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