| pubmed-article:17371811 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C0019682 | lld:lifeskim |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C0033607 | lld:lifeskim |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:17371811 | lifeskim:mentions | umls-concept:C1959366 | lld:lifeskim |
| pubmed-article:17371811 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:17371811 | pubmed:dateCreated | 2007-5-22 | lld:pubmed |
| pubmed-article:17371811 | pubmed:abstractText | We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC(50)], 0.0002 to 0.0005 microM) with minimal cytotoxicity (50% cytotoxicity, 35.7 microM in CD4(+) MT-2 cells). GRL-98065 blocked the infectivity and replication of each of the HIV-1(NL4-3) variants exposed to and selected by up to a 5 microM concentration of saquinavir, indinavir, nelfinavir, or ritonavir and a 1 microM concentration of lopinavir or atazanavir (EC(50), 0.0015 to 0.0075 microM), although it was less active against HIV-1(NL4-3) selected by amprenavir (EC(50), 0.032 microM). GRL-98065 was also potent against multiple-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents, HIV-1 isolates of various subtypes, and HIV-2 isolates examined. Structural analyses revealed that the close contact of GRL-98065 with the main chain of the protease active-site amino acids (Asp29 and Asp30) is important for its potency and wide-spectrum activity against multiple-PI-resistant HIV-1 variants. The present data demonstrate that the privileged nonpeptide P2 ligand, bis-THF, is critical for the binding of GRL-98065 to the HIV protease substrate binding site and that this scaffold can confer highly potent antiviral activity against a wide spectrum of HIV isolates. | lld:pubmed |
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| pubmed-article:17371811 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:17371811 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17371811 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17371811 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:17371811 | pubmed:issn | 0066-4804 | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:MitsuyaHiroak... | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:GhoshArun KAK | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:KohYasuhiroY | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:LiJianfengJ | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:WangYuan-Fang... | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:WeberIrene... | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:BorossPeter... | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:DasDebanandaD | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:AmanoMasayuki... | lld:pubmed |
| pubmed-article:17371811 | pubmed:author | pubmed-author:LeschenkoSofi... | lld:pubmed |
| pubmed-article:17371811 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17371811 | pubmed:volume | 51 | lld:pubmed |
| pubmed-article:17371811 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17371811 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17371811 | pubmed:pagination | 2143-55 | lld:pubmed |
| pubmed-article:17371811 | pubmed:dateRevised | 2010-8-24 | lld:pubmed |
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| pubmed-article:17371811 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17371811 | pubmed:articleTitle | A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. | lld:pubmed |
| pubmed-article:17371811 | pubmed:affiliation | Departments of Infectious Diseases and Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan. | lld:pubmed |
| pubmed-article:17371811 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17371811 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:17371811 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:17371811 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| pubmed-article:17371811 | pubmed:publicationType | Research Support, N.I.H., Intramural | lld:pubmed |
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