PRX-08066 (original) (raw)

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Chemical compound

Pharmaceutical compound

PRX-08066
Identifiers
IUPAC name 5-((4-(6-chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile
CAS Number 866206-54-4 checkY
PubChem CID 11502243
ChemSpider 9677045
UNII 82SK298EBU
CompTox Dashboard (EPA) DTXSID60235710 Edit this at Wikidata
Chemical and physical data
Formula C19H17ClFN5S
Molar mass 401.89 g·mol−1
3D model (JSmol) Interactive image
SMILES s3c2ncnc(c2cc3Cl)NC4CCN(CC4)Cc(ccc1F)cc1C#N

PRX-08066 is a drug discovered and developed by Predix (later Epix) Pharmaceuticals [Dale S. Dhanoa et al. Patent US 7,030,240 B2], which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with a 5-HT2B binding affinity (Ki) of 3.4nM, and high selectivity over the closely related 5-HT2A and 5-HT2C receptors and other receptor targets. PRX-08066 and other selective 5-HT2B antagonists are being researched for the treatment of pulmonary arterial hypertension, following the discovery that the potent 5-HT2B agonist norfenfluramine produces pulmonary arterial hypertension and subsequent heart valve damage. 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.[1] It is also being researched for potential anti-cancer applications, due to its ability to inhibit fibroblast activation.[2]

  1. ^ Porvasnik SL, Germain S, Embury J, Gannon KS, Jacques V, Murray J, Byrne BJ, Shacham S, Al-Mousily F (August 2010). "PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats". The Journal of Pharmacology and Experimental Therapeutics. 334 (2): 364–72. doi:10.1124/jpet.109.165001. PMID 20430844. S2CID 206500649.
  2. ^ Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R, Modlin IM (June 2010). "The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment". Cancer. 116 (12): 2902–12. doi:10.1002/cncr.25049. PMID 20564397.