# Zaprinast

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Zaprinast
> Markdown URL: https://mediated.wiki/source/Zaprinast.md
> Source: https://en.wikipedia.org/wiki/Zaprinast
> Source revision: 1329901837
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{chembox
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| ImageFile = Zaprinast.svg
| ImageClass = skin-invert-image
| ImageSize = 150
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| IUPACName = 5-(2-Propoxyphenyl)-1''H''-[1,2,3]triazolo[4,5-d]pyrimidin-7(4''H'')-one
| OtherNames = M&B 22,948

| Section1 = {{Chembox Identifiers
| IUPHAR_ligand = 2919
| CASNo = 37762-06-4
| CASNo_Ref = {{cascite|changed|??}}
| PubChem = 135399235
| ChEBI = 92215
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5520
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 28079
| EINECS = 253-655-1
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| StdInChIKey = REZGGXNDEMKIQB-UHFFFAOYSA-N
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| StdInChI=1S/C13H13N5O2/c1-2-7-20-9-6-4-3-5-8(9)11-14-12-10(13(19)15-11)16-18-17-12/h3-6H,2,7H2,1H3,(H2,14,15,16,17,18,19)
| SMILES = O=C1C2=C(N=NN2)NC(C3=CC=CC=C3OCCC)=N1
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| UNII = GXT25D5DS0
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| Section2 = {{Chembox Properties
| C=13 | H=13 | N=5 | O=2 
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| Section5 = {{Chembox Pharmacology
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'''Zaprinast''' was an unsuccessful clinical drug candidate that was a precursor to the chemically related [PDE5 inhibitor](/source/PDE5_inhibitor)s, such as [sildenafil](/source/sildenafil) (Viagra), which successfully reached the market. It is a [phosphodiesterase inhibitor](/source/phosphodiesterase_inhibitor),<ref>{{cite journal | last1 = Choi | first1 = SH | last2 = Choi | first2 = DH | last3 = Song | first3 = KS | last4 = Shin | first4 = KH | last5 = Chun | first5 = BG | title = Zaprinast, an inhibitor of cGMP-selective phosphodiesterases, enhances the secretion of TNF-alpha and IL-1beta and the expression of iNOS and MHC class II molecules in rat microglial cells | journal = Journal of Neuroscience Research | volume = 67 | issue = 3 | pages = 411–21 | year = 2002 | pmid = 11813247 | doi = 10.1002/jnr.10102 | s2cid = 24513289 }}</ref> selective for the subtypes [PDE5](/source/CGMP-specific_phosphodiesterase_type_5), [PDE6](/source/PDE6), [PDE9](/source/PDE9) and [PDE11](/source/PDE11).  [IC<sub>50</sub>](/source/IC50) values are 0.76, 0.15, 29.0, and 12.0 ''μ''M, respectively.<ref>{{Cite journal 
| last1 = Taniguchi | first1 = Y. 
| last2 = Tonaikachi | first2 = H. 
| last3 = Shinjo | first3 = K. 
| doi = 10.1016/j.febslet.2006.08.015 
| title = Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35 
| journal = FEBS Letters 
| volume = 580 
| issue = 21 
| pages = 5003–5008 
| year = 2006 
| pmid = 16934253 
| pmc = 
| bibcode = 2006FEBSL.580.5003T 
| s2cid = 43142927 
}}</ref><ref>{{Cite journal 
| last1 = Keswani | first1 = A. N. 
| last2 = Peyton | first2 = K. J. 
| last3 = Durante | first3 = W. 
| last4 = Schafer | first4 = A. I. 
| last5 = Tulis | first5 = D. A. 
| title = The Cyclic GMP Modulators YC-1 and Zaprinast Reduce Vessel Remodeling Through Antiproliferative and Proapoptotic Effects 
| doi = 10.1177/1074248409333266 
| journal = Journal of Cardiovascular Pharmacology and Therapeutics 
| volume = 14 
| issue = 2 
| pages = 116–124 
| year = 2009 
| pmid = 19342499 
| pmc =2702762 
}}</ref>

Zaprinast inhibits the growth of asexual blood-stage [malaria](/source/malaria) parasites ([''P. falciparum''](/source/Plasmodium_falciparum)) ''in vitro'' with an [ED<sub>50</sub>](/source/ED-50) value of 35 ''μ''M, and inhibits PfPDE1, a ''[P. falciparum](/source/P._falciparum)'' cGMP-specific phosphodiesterase, with an IC<sub>50</sub> value of 3.8 ''μ''M.<ref>{{Cite journal|title = PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum|author1=Keizo Yuasa |author2=Fumika Mi-Ichi |author3=Tamaki Kobayashi |author4=Masaya Yamanouchi |author5=Jun Kotera |author6=Kiyoshi Kita |author7=Kenji Omori |date = 2005|journal = Biochem. J.|doi = 10.1042/BJ20050425|pmid = 16038615|pmc=1317681|volume=392|issue=Pt 1 |pages=221–9}}</ref>

Zaprinast has also been shown to activate the orphan [G-protein coupled receptor](/source/G-protein_coupled_receptor) known as [GPR35](/source/GPR35), both in rats and humans,<ref>{{cite journal|journal = FEBS Letters|title = Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35|author1=Yasuhito Taniguchi |author2=Hiroko Tonai-Kachi |author3=Katsuhiro Shinjo |volume = 580|issue = 21|pages = 5003–5008|year = 2006|doi=10.1016/j.febslet.2006.08.015|pmid=16934253| bibcode=2006FEBSL.580.5003T |s2cid = 43142927}}</ref> and to inhibit the mitochondrial [pyruvate](/source/pyruvate) carrier.<ref>{{cite journal|journal = J Biol Chem|title = Inhibition of mitochondrial pyruvate transport by zaprinast causes massive accumulation of aspartate at the expense of glutamate in the retina|author1=Jianhai Du |author2=Whitney M Cleghorn |author3=Laura Contreras |author4=Ken Lindsay |author5=Austin M Rountree |author6=Andrei O Chertov |author7=Sally J Turner |author8=Ayse Sahaboglu |author9=Jonathan Linton |author10=Martin Sadilek |author11=Jorgina Satrustegui |author12=Ian R Sweet |author13=Francois Paquet-Durand |author14=James B Hurley |volume = 288|issue = 50|pages = 36129–36140|year = 2013|doi=10.1074/jbc.M113.507285|pmid=24187136|s2cid = 9429684|pmc=3861660 |doi-access = free}}</ref> 

==References==
{{reflist}}

{{Phosphodiesterase inhibitors}}

Category:Abandoned drugs
Category:Phosphodiesterase inhibitors
Category:PDE5 inhibitors
Category:Propoxy compounds
Category:Triazolopyrimidines
Category:Lactams

{{pharma-stub}}

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Adapted from the Wikipedia article [Zaprinast](https://en.wikipedia.org/wiki/Zaprinast) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Zaprinast?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.