1HXW

HIV-1 PROTEASE DIMER COMPLEXED WITH A-84538

Summary for 1HXW

• Entry DOI: 10.2210/pdb1hxw/pdb
• Related PRD ID: PRD_001001
• Descriptor: HIV-1 PROTEASE, RITONAVIR (3 entities in total)
• Functional Keywords: aspartyl protease, hydrolase, aspartic proteinase, hiv, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12499
• Total number of polymer chains: 2
• Total formula weight: 22382.51

Authors

Park, C.H.,Nienaber, V.,Kong, X.P. (deposition date: 1997-01-24, release date: 1998-02-04, Last modification date: 2024-02-07)

Primary citation

Kempf, D.J.,Marsh, K.C.,Denissen, J.F.,McDonald, E.,Vasavanonda, S.,Flentge, C.A.,Green, B.E.,Fino, L.,Park, C.H.,Kong, X.P.
ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans.
Proc.Natl.Acad.Sci.USA, 92:2484-2488, 1995

PubMed Abstract: 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% effective concentration (EC50) = 0.022-0.13 microM] 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.

PubMed: 7708670
DOI: 10.1073/pnas.92.7.2484

Experimental method

X-RAY DIFFRACTION (1.8 Å)