Future directions in phosphodiesterase drug discovery
Research on phosphodiesterases both in academic labs and in the pharmaceutical industry has remained steady over the past 35 years. Although there have been some clinical successes, they have been clustered around just a couple of PDE isoforms, and disproportionate to the huge investment put forth a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-11, Vol.22 (22), p.6794-6800 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | DeNinno, Michael P. |
| description | Research on phosphodiesterases both in academic labs and in the pharmaceutical industry has remained steady over the past 35 years. Although there have been some clinical successes, they have been clustered around just a couple of PDE isoforms, and disproportionate to the huge investment put forth against what seem like very druggable targets. This review attempts to uncover the reasons for the lack of productivity in PDE drug discovery, and summarizes the current hot areas of research. In addition, new insights gathered about structure–function relationships are highlighted, in particular those relating to enzyme regulation. Lastly, novel strategies for targeting the activation or inactivation of selected PDEs are proposed that may allow for a more targeted approach for PDE modulation. |
| doi_str_mv | 10.1016/j.bmcl.2012.09.028 |
| format | Article |
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Drug treatments</subject><subject>Phosphodiesterase</subject><subject>Phosphodiesterase Inhibitors - chemistry</subject><subject>Phosphodiesterase Inhibitors - metabolism</subject><subject>Phosphoric Diester Hydrolases - chemistry</subject><subject>Phosphoric Diester Hydrolases - metabolism</subject><subject>Protein Binding</subject><subject>Protein Isoforms - antagonists & inhibitors</subject><subject>Protein Isoforms - metabolism</subject><subject>Regulatory domain</subject><subject>Splice variants</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEURYMotlb_gAvpRnAz48vHpBNwI8WqUHCj4C5kkoymzEdNZgr992aYqjsXjyzeeZebg9AlhhQD5rebtKh1lRLAJAWRAsmP0BQzzhLKIDtGUxAcklyw9wk6C2EDgBkwdoomhALjgpMpylZ913s7N85b3bm2CXPXzLefbYhjnA2d9SrEve8_IhR0u7N-f45OSlUFe3F4Z-ht9fC6fErWL4_Py_t1ohmFLikJxUrkuaJEcVMawfiCLhQAsbjIi6wsMAeqTK6LwhjCsKYkw8QqyArKhKIzdDPmbn371ccyso4VbFWpxrZ9kBjj4R8QU2aIjKj2bQjelnLrXa38XmKQgy65kYMuOeiSIGTUFY-uDvl9UVvze_LjJwLXB0AFrarSq0a78MfxTFDIFpG7Gzkbbeyc9TJoZxttR6_StO6_Ht8ZhYg1</recordid><startdate>20121115</startdate><enddate>20121115</enddate><creator>DeNinno, Michael P.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20121115</creationdate><title>Future directions in phosphodiesterase drug discovery</title><author>DeNinno, Michael P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-f231a988a32a6dfd946737a002e1b8b5fb1603ad8cbbdd241c32512ea05b349a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Allosteric Regulation</topic><topic>Biological and medical sciences</topic><topic>cAMP</topic><topic>Catalytic Domain</topic><topic>cGMP</topic><topic>Drug Evaluation, Preclinical</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphodiesterase</topic><topic>Phosphodiesterase Inhibitors - chemistry</topic><topic>Phosphodiesterase Inhibitors - metabolism</topic><topic>Phosphoric Diester Hydrolases - chemistry</topic><topic>Phosphoric Diester Hydrolases - metabolism</topic><topic>Protein Binding</topic><topic>Protein Isoforms - antagonists & inhibitors</topic><topic>Protein Isoforms - metabolism</topic><topic>Regulatory domain</topic><topic>Splice variants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DeNinno, Michael P.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DeNinno, Michael P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Future directions in phosphodiesterase drug discovery</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2012-11-15</date><risdate>2012</risdate><volume>22</volume><issue>22</issue><spage>6794</spage><epage>6800</epage><pages>6794-6800</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Research on phosphodiesterases both in academic labs and in the pharmaceutical industry has remained steady over the past 35 years. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2012-11, Vol.22 (22), p.6794-6800 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Allosteric Regulation Biological and medical sciences cAMP Catalytic Domain cGMP Drug Evaluation, Preclinical Medical sciences Pharmacology. Drug treatments Phosphodiesterase Phosphodiesterase Inhibitors - chemistry Phosphodiesterase Inhibitors - metabolism Phosphoric Diester Hydrolases - chemistry Phosphoric Diester Hydrolases - metabolism Protein Binding Protein Isoforms - antagonists & inhibitors Protein Isoforms - metabolism Regulatory domain Splice variants |
| title | Future directions in phosphodiesterase drug discovery |
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