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PDBsum entry 1hxw
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Hydrolase/hydrolase inhibitor
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PDB id
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1hxw
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Abt-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans.
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Authors
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D.J.Kempf,
K.C.Marsh,
J.F.Denissen,
E.Mcdonald,
S.Vasavanonda,
C.A.Flentge,
B.E.Green,
L.Fino,
C.H.Park,
X.P.Kong.
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Ref.
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Proc Natl Acad Sci U S A, 1995,
92,
2484-2488.
[DOI no: ]
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PubMed id
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Abstract
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Examination of the structural basis for antiviral activity, oral
pharmacokinetics, and hepatic metabolism among a series of symmetry-based
inhibitors of the human immunodeficiency virus (HIV) protease led to the
discovery of ABT-538, a promising experimental drug for the therapeutic
intervention in acquired immunodeficiency syndrome (AIDS). ABT-538 exhibited
potent in vitro activity against laboratory and clinical strains of HIV-1 [50%
and HIV-2 (EC50 = 0.16
microM). Following a single 10-mg/kg oral dose, plasma concentrations in rat,
dog, and monkey exceeded the in vitro antiviral EC50 for > 12 h. In human
trials, a single 400-mg dose of ABT-538 displayed a prolonged absorption profile
and achieved a peak plasma concentration in excess of 5 micrograms/ml. These
findings demonstrate that high oral bioavailability can be achieved in humans
with peptidomimetic inhibitors of HIV protease.
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