Zaprinast was an unsuccessful clinical drug candidate that was a precursor to the chemically related PDE5 inhibitors, such as sildenafil (Viagra), which successfully reached the market. It is a phosphodiesterase inhibitor,[1] selective for the subtypes PDE5, PDE6, PDE9 and PDE11. IC50 values are 0.76, 0.15, 29.0, and 12.0 μM, respectively.[2][3]
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| Names | |
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| IUPAC name
5-(2-Propoxyphenyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-7(4H)-one
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| Other names
M&B 22,948
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| Identifiers | |
3D model (JSmol)
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.048.760 |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C13H13N5O2 | |
| Molar mass | 271.280 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Zaprinast inhibits the growth of asexual blood-stage malaria parasites (P. falciparum) in vitro with an ED50 value of 35 μM, and inhibits PfPDE1, a P. falciparum cGMP-specific phosphodiesterase, with an IC50 value of 3.8 μM.[4]
Zaprinast has also been shown to activate the orphan G-protein coupled receptor known as GPR35, both in rats and humans,[5] and to inhibit the mitochondrial pyruvate carrier. [6]
References
edit- ^ Choi, SH; Choi, DH; Song, KS; Shin, KH; Chun, BG (2002). "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 of Neuroscience Research. 67 (3): 411–21. doi:10.1002/jnr.10102. PMID 11813247. S2CID 24513289.411-21&rft.date=2002&rft_id=https://api.semanticscholar.org/CorpusID:24513289#id-name=S2CID&rft_id=info:pmid/11813247&rft_id=info:doi/10.1002/jnr.10102&rft.aulast=Choi&rft.aufirst=SH&rft.au=Choi, DH&rft.au=Song, KS&rft.au=Shin, KH&rft.au=Chun, BG&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
- ^ Taniguchi, Y.; Tonaikachi, H.; Shinjo, K. (2006). "Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35". FEBS Letters. 580 (21): 5003–5008. doi:10.1016/j.febslet.2006.08.015. PMID 16934253. S2CID 43142927.5003-5008&rft.date=2006&rft_id=https://api.semanticscholar.org/CorpusID:43142927#id-name=S2CID&rft_id=info:pmid/16934253&rft_id=info:doi/10.1016/j.febslet.2006.08.015&rft.aulast=Taniguchi&rft.aufirst=Y.&rft.au=Tonaikachi, H.&rft.au=Shinjo, K.&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
- ^ Keswani, A. N.; Peyton, K. J.; Durante, W.; Schafer, A. I.; Tulis, D. A. (2009). "The Cyclic GMP Modulators YC-1 and Zaprinast Reduce Vessel Remodeling Through Antiproliferative and Proapoptotic Effects". Journal of Cardiovascular Pharmacology and Therapeutics. 14 (2): 116–124. doi:10.1177/1074248409333266. PMC 2702762. PMID 19342499.116-124&rft.date=2009&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702762#id-name=PMC&rft_id=info:pmid/19342499&rft_id=info:doi/10.1177/1074248409333266&rft.aulast=Keswani&rft.aufirst=A. N.&rft.au=Peyton, K. J.&rft.au=Durante, W.&rft.au=Schafer, A. I.&rft.au=Tulis, D. A.&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702762&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
- ^ Keizo Yuasa; Fumika Mi-Ichi; Tamaki Kobayashi; Masaya Yamanouchi; Jun Kotera; Kiyoshi Kita; Kenji Omori (2005). "PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum". Biochem. J. 392 (Pt 1): 221–9. doi:10.1042/BJ20050425. PMC 1317681. PMID 16038615.221-9&rft.date=2005&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1317681#id-name=PMC&rft_id=info:pmid/16038615&rft_id=info:doi/10.1042/BJ20050425&rft.au=Keizo Yuasa&rft.au=Fumika Mi-Ichi&rft.au=Tamaki Kobayashi&rft.au=Masaya Yamanouchi&rft.au=Jun Kotera&rft.au=Kiyoshi Kita&rft.au=Kenji Omori&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1317681&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
- ^ Yasuhito Taniguchi; Hiroko Tonai-Kachi; Katsuhiro Shinjo (2006). "Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35". FEBS Letters. 580 (21): 5003–5008. doi:10.1016/j.febslet.2006.08.015. PMID 16934253. S2CID 43142927.5003-5008&rft.date=2006&rft_id=https://api.semanticscholar.org/CorpusID:43142927#id-name=S2CID&rft_id=info:pmid/16934253&rft_id=info:doi/10.1016/j.febslet.2006.08.015&rft.au=Yasuhito Taniguchi&rft.au=Hiroko Tonai-Kachi&rft.au=Katsuhiro Shinjo&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
- ^ Jianhai Du; Whitney M Cleghorn; Laura Contreras; Ken Lindsay; Austin M Rountree; Andrei O Chertov; Sally J Turner; Ayse Sahaboglu; Jonathan Linton; Martin Sadilek; Jorgina Satrustegui; Ian R Sweet; Francois Paquet-Durand; James B Hurley (2013). "Inhibition of mitochondrial pyruvate transport by zaprinast causes massive accumulation of aspartate at the expense of glutamate in the retina". J Biol Chem. 288 (50): 36129–36140. doi:10.1074/jbc.M113.507285. PMC 3861660. PMID 24187136. S2CID 9429684.36129-36140&rft.date=2013&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861660#id-name=PMC&rft_id=https://api.semanticscholar.org/CorpusID:9429684#id-name=S2CID&rft_id=info:pmid/24187136&rft_id=info:doi/10.1074/jbc.M113.507285&rft.au=Jianhai Du&rft.au=Whitney M Cleghorn&rft.au=Laura Contreras&rft.au=Ken Lindsay&rft.au=Austin M Rountree&rft.au=Andrei O Chertov&rft.au=Sally J Turner&rft.au=Ayse Sahaboglu&rft.au=Jonathan Linton&rft.au=Martin Sadilek&rft.au=Jorgina Satrustegui&rft.au=Ian R Sweet&rft.au=Francois Paquet-Durand&rft.au=James B Hurley&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861660&rfr_id=info:sid/en.wikipedia.org:Zaprinast" class="Z3988">
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