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Details

Stereochemistry ACHIRAL
Molecular Formula C19H17ClFN5S
Molecular Weight 401.888
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PRX-08066 FREE BASE

SMILES

FC1=CC=C(CN2CCC(CC2)NC3=C4C=C(Cl)SC4=NC=N3)C=C1C#N

InChI

InChIKey=IENZFHBNCRQMNP-UHFFFAOYSA-N
InChI=1S/C19H17ClFN5S/c20-17-8-15-18(23-11-24-19(15)27-17)25-14-3-5-26(6-4-14)10-12-1-2-16(21)13(7-12)9-22/h1-2,7-8,11,14H,3-6,10H2,(H,23,24,25)

HIDE SMILES / InChI

Molecular Formula C19H17ClFN5S
Molecular Weight 401.888
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. This drug was discovered and developed by Predix (later Epix) Pharmaceuticals and is being researched for the treatment of pulmonary arterial hypertension. In animal studies, PRX-08066 has been found to reduce several key indicators of pulmonary arterial hypertension and improved cardiac output, with similar efficacy to established drugs for this condition such as bosentan, sildenafil, beraprost and iloprost.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.4 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats.
2010 Aug
Patents

Patents

Sample Use Guides

in rats: twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks.
Route of Administration: Oral
It was investigated properties of PRX-08066 in NET cell lines (KRJ-I, H720) and in the coculture system (KRJ-I cells: fibroblastic HEK293 cells) using real time polymerase chain reaction, ELISA, Ki67 immunostaining, and flow cytometry-based caspase 3 assays to assess antiproliferative and profibrotic signaling pathways. PRX-08066 inhibited proliferation (IC(50) 4.6 x 10(-9)M) and 5-HT secretion (6.9 x 10(-9)M) and decreased ERK1/2 phosphorylation and profibrotic growth factor synthesis and secretion (transforming growth factor beta 1 [TGFbeta1], connective tissue growth factor [CTGF] and fibroblast growth factor [FGF2]). In the KRJ-I:HEK293 coculture system, PRX-08066 significantly decreased 5-HT release (>60%), Ki67 (transcript and immunostaining: 20%-80%), TGFbeta1, CTGF, and FGF2 transcription (20%-50%) in the KRJ-I cell line. 5-HT itself stimulated HEK293 proliferation (25%) and synthesis of TGFbeta1, CTGF and FGF2. PRX-08066 inhibition of KRJ-I function reversed these effects in the coculture system.
Substance Class Chemical
Created
by admin
on Sat Dec 16 02:17:44 UTC 2023
Edited
by admin
on Sat Dec 16 02:17:44 UTC 2023
Record UNII
82SK298EBU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PRX-08066 FREE BASE
Common Name English
BENZONITRILE, 5-((4-((6-CHLOROTHIENO(2,3-D)PYRIMIDIN-4-YL)AMINO)-1-PIPERIDINYL)METHYL)-2-FLUORO-
Systematic Name English
5-((4-(6-CHLOROTHIENO(2,3-D)PYRIMIDINE-4-YLAMINO)PIPERIDIN-1-YL)METHYL)-2-FLUOROBENZONITRILE
Systematic Name English
Code System Code Type Description
WIKIPEDIA
PRX-08066
Created by admin on Sat Dec 16 02:17:44 UTC 2023 , Edited by admin on Sat Dec 16 02:17:44 UTC 2023
PRIMARY
CAS
866206-54-4
Created by admin on Sat Dec 16 02:17:44 UTC 2023 , Edited by admin on Sat Dec 16 02:17:44 UTC 2023
PRIMARY
PUBCHEM
11502243
Created by admin on Sat Dec 16 02:17:44 UTC 2023 , Edited by admin on Sat Dec 16 02:17:44 UTC 2023
PRIMARY
EPA CompTox
DTXSID60235710
Created by admin on Sat Dec 16 02:17:44 UTC 2023 , Edited by admin on Sat Dec 16 02:17:44 UTC 2023
PRIMARY
FDA UNII
82SK298EBU
Created by admin on Sat Dec 16 02:17:44 UTC 2023 , Edited by admin on Sat Dec 16 02:17:44 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Ki
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY