| pubmed-article:20409721 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0033262 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0028621 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1955880 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1999216 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1880355 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C2698650 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0260127 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C0718463 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C2352228 | lld:lifeskim |
| pubmed-article:20409721 | lifeskim:mentions | umls-concept:C1957245 | lld:lifeskim |
| pubmed-article:20409721 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:20409721 | pubmed:dateCreated | 2010-5-12 | lld:pubmed |
| pubmed-article:20409721 | pubmed:abstractText | GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosphonic acid] 4 is a novel nucleoside phosphonate HIV-1 reverse transcriptase (RT) inhibitor with a unique resistance profile toward N(t)RTI resistance mutations. To effectively deliver 4 and its active phosphorylated metabolite 15 into target cells, a series of amidate prodrugs were designed as substrates of cathepsin A, an intracellular lysosomal carboxypeptidase highly expressed in peripheral blood mononuclear cells (PBMCs). The ethylalaninyl phosphonamidate prodrug 5 (GS-9131) demonstrated favorable cathepsin A substrate properties, in addition to favorable in vitro intestinal and hepatic stabilities. Following oral dosing (3mg/kg) in Beagle dogs, high levels (>9.0microM) of active metabolite 15 were observed in PBMCs, validating the prodrug design process and leading to the nomination of 5 as a clinical candidate. | lld:pubmed |
| pubmed-article:20409721 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20409721 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20409721 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20409721 | pubmed:month | May | lld:pubmed |
| pubmed-article:20409721 | pubmed:issn | 1464-3391 | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:CihlarTomasT | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:GaoYingY | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:BirkusGabriel... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:RayAdrian SAS | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:ZhangLijunL | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:MackmanRichar... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:HuiHon CHC | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:DouglasJanet... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:LinKuei-YingK... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:BoojamraConst... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:DesaiManoj... | lld:pubmed |
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| pubmed-article:20409721 | pubmed:author | pubmed-author:GrantDeborahD | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:MarkevitchDav... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:PakdamanRowch... | lld:pubmed |
| pubmed-article:20409721 | pubmed:author | pubmed-author:MishraRuchika... | lld:pubmed |
| pubmed-article:20409721 | pubmed:copyrightInfo | Copyright 2010 Elsevier Ltd. All rights reserved. | lld:pubmed |
| pubmed-article:20409721 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20409721 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:20409721 | pubmed:volume | 18 | lld:pubmed |
| pubmed-article:20409721 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20409721 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20409721 | pubmed:pagination | 3606-17 | lld:pubmed |
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| pubmed-article:20409721 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20409721 | pubmed:articleTitle | Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148. | lld:pubmed |
| pubmed-article:20409721 | pubmed:affiliation | Department of Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA94404, USA. Richard.Mackman@gilead.com | lld:pubmed |
| pubmed-article:20409721 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:20409721 | lld:chembl |
