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
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)
| 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
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
Edited
Sat Dec 16 02:17:44 GMT 2023
by
admin
on
Sat Dec 16 02:17:44 GMT 2023
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| Record UNII |
82SK298EBU
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| Record Status |
Validated (UNII)
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| Record Version |
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PRX-08066
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866206-54-4
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11502243
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DTXSID60235710
Created by
admin on Sat Dec 16 02:17:44 GMT 2023 , Edited by admin on Sat Dec 16 02:17:44 GMT 2023
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82SK298EBU
Created by
admin on Sat Dec 16 02:17:44 GMT 2023 , Edited by admin on Sat Dec 16 02:17:44 GMT 2023
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| Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
Ki
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SALT/SOLVATE -> PARENT |
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
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