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
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15146030 | https://www.ncbi.nlm.nih.gov/pubmed/23904152Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800014355
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
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
2000 mg single, oral (unknown) Highest studied dose |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
Other AEs: diarrhea, Fatigue... Other AEs: diarrhea (1 pt) Sources: Fatigue (1 pt) Fatigue (2 patients) vomiting (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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
Other AEs: Dyspepsia, headache... Other AEs: Dyspepsia (1 pt) Sources: 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) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Fatigue | 1 pt | 2000 mg single, oral (unknown) Highest studied dose |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
diarrhea | 1 pt | 2000 mg single, oral (unknown) Highest studied dose |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
Fatigue | 2 patients | 2000 mg single, oral (unknown) Highest studied dose |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
vomiting | 2 patients | 2000 mg single, oral (unknown) Highest studied dose |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
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: |
healthy n = 6 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 6 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients. | 2006 Sep |
|
Role of urotensin II and its receptor in health and disease. | 2007 |
|
Non peptidic urotensin II antagonists: perspectives for a new class of drugs. | 2008 Apr |
|
Urotensin II and urotensin II-related peptide activate somatostatin receptor subtypes 2 and 5. | 2008 May |
|
Cardiorenovascular effects of urotensin II and the relevance of the UT receptor. | 2008 May |
|
Evidence for endogenous urotensin-II as an inhibitor of insulin secretion. Study in the perfused rat pancreas. | 2008 May |
|
Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus. | 2009 Oct |
|
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 |
|
Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy. | 2010 May |
|
Expression of urotensin II and its receptor in human liver cirrhosis and fulminant hepatic failure. | 2010 May |
|
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
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15146030
1 uM palosuran significantly decreased Urotensin-II induced contraction of rat aortic rings
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29707
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300000036961
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C66298
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DTXSID00202406
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CHEMBL567303
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540769-28-6
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10173280
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C493249
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ACTIVE MOIETY