BIOMAT Database Logo BIOMAT Database Logo

In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV. 2007

Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Department of Virology, GlaxoSmithKline, 5 Moore Dr., P.O. Box 13398, Research Triangle Park, NC 27709, USA. richard.j.hazen@gsk.com

Brecanavir, a novel tyrosyl-based arylsulfonamide, high-affinity, human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), has been evaluated for anti-HIV activity in several in vitro assays. Preclinical assessment of brecanavir indicated that this compound potently inhibited HIV-1 in cell culture assays with 50% effective concentrations (EC(50)s) of 0.2 to 0.53 nM and was equally active against HIV strains utilizing either the CXCR4 or CCR5 coreceptor, as was found with other PIs. The presence of up to 40% human serum decreased the anti-HIV-1 activity of brecanavir by 5.2-fold, but under these conditions the compound retained single-digit nanomolar EC(50)s. When brecanavir was tested in combination with nucleoside reverse transcriptase inhibitors, the antiviral activity of brecanavir was synergistic with the effects of stavudine and additive to the effects of zidovudine, tenofovir, dideoxycytidine, didanosine, adefovir, abacavir, lamivudine, and emtricitabine. Brecanavir was synergistic with the nonnucleoside reverse transcriptase inhibitor nevirapine or delavirdine and was additive to the effects of efavirenz. In combination with other PIs, brecanavir was additive to the activities of indinavir, lopinavir, nelfinavir, ritonavir, amprenavir, saquinavir, and atazanavir. Clinical HIV isolates from PI-experienced patients were evaluated for sensitivity to brecanavir and other PIs in a recombinant virus assay. Brecanavir had a <5-fold increase in EC(50)s against 80% of patient isolates tested and had a greater mean in vitro potency than amprenavir, indinavir, lopinavir, atazanavir, tipranavir, and darunavir. Brecanavir is by a substantial margin the most potent and broadly active antiviral agent among the PIs tested in vitro.

UI MeSH Term Description Entries
D009961 Orosomucoid Acid Seromucoid,Seromucoid,Serum Sialomucin,alpha 1-Acid Glycoprotein,alpha 1-Acid Seromucoid,A(1)-Acid Seromucoid,Acid alpha 1-Glycoprotein,Alpha(1)-Acid Glycoprotein,alpha 1-Acid Glycoprotein (Acute Phase),alpha 1-Glycoprotein Acid,Acid alpha 1 Glycoprotein,Glycoprotein, alpha 1-Acid,Seromucoid, Acid,Seromucoid, alpha 1-Acid,Sialomucin, Serum,alpha 1 Acid Glycoprotein,alpha 1 Acid Seromucoid,alpha 1 Glycoprotein Acid
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002219 Carbamates Derivatives of carbamic acid, H2NC( Carbamate,Aminoformic Acids,Carbamic Acids,Acids, Aminoformic,Acids, Carbamic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D012709 Serum Albumin A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules. Plasma Albumin,Albumin, Serum
D014443 Tyrosine A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin. L-Tyrosine,Tyrosine, L-isomer,para-Tyrosine,L Tyrosine,Tyrosine, L isomer,para Tyrosine

Related Publications

Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Antiviral activity of UIC-PI, a novel inhibitor of the human immunodeficiency virus type 1 protease.
April 2002, Antiviral research,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Single-dose safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus protease inhibitor.
June 2006, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1.
November 2007, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.
October 1997, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor.
December 1993, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates.
November 1997, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Antiviral activity and cross-resistance profile of P-1946, a novel human immunodeficiency virus type 1 protease inhibitor.
June 2006, Antiviral research,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates.
June 2005, Antimicrobial agents and chemotherapy,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Antiviral activity of Hawaiian medicinal plants against human immunodeficiency Virus Type-1 (HIV-1).
January 1996, Phytomedicine : international journal of phytotherapy and phytopharmacology,
Richard Hazen, and Robert Harvey, and Robert Ferris, and Charles Craig, and Phillip Yates, and Philip Griffin, and John Miller, and Istvan Kaldor, and John Ray, and Vincente Samano, and Eric Furfine, and Andrew Spaltenstein, and Michael Hale, and Roger Tung, and Marty St Clair, and Mary Hanlon, and Lawrence Boone
Antiviral activity of fattiviracin FV-8 against human immunodeficiency virus type 1 (HIV-1).
March 2001, Bioscience, biotechnology, and biochemistry,
Copied contents to your clipboard!