Abstract:
:To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily as a consequence of poor oral bioavailability in animal models. L-735,524 represents a class of human immunodeficiency virus type 1 protease inhibitors, termed hydroxyaminopentane amides, that incorporate a basic amine into the hydroxyethylene inhibitor backbone. L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles. The compound is effective against viruses resistant to reverse transcriptase inhibitors and is synergistically active when used in combination with reverse transcriptase inhibitors. Most importantly, L-735,524 exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals by using clinically acceptable formulations. Accordingly, the compound was selected for evaluation of safety and pharmacokinetic studies in humans.
journal_name
Proc Natl Acad Sci U S Aauthors
Vacca JP,Dorsey BD,Schleif WA,Levin RB,McDaniel SL,Darke PL,Zugay J,Quintero JC,Blahy OM,Roth Edoi
10.1073/pnas.91.9.4096subject
Has Abstract,Author List Incompletepub_date
1994-04-26 00:00:00pages
4096-100issue
9eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::The conversion of cells from a normal phenotype to full malignancy apparently requires multiple genetic events. Efforts to reconstruct multistep tumorigenesis in cell culture have shown that two types of oncogenes (typified by HRAS and MYC) can cooperate to elicit complete transformation. Transformation of embryonic r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2008-08-12 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1978-06-01 00:00:00
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更新日期:2007-12-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1996-05-14 00:00:00