Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails

Journal of Acquired Immune Deficiency Syndromes

Volumn 29, Issue 1, 2002, Pages 11-20

  Mewshaw, Jennifer P ^a   Myrick, Florence T ^a   Wakefield, Debby A C S ^a   Hooper, Brandi J ^a   Harris, Jeanette L ^a   McCreedy, Bruce ^a   Borroto Esoda, Katyna ^a  

^a Triangle Pharmaceuticals   (United States)

Author keywords

( ) D 2,6 Diaminopurine dioxolane (DAPD); ( ) D Dioxolane guanosine (DXG); 50 Cytotoxic dose (CC50); HIV 1 50 Effective concentration (EC50); Multidrug resistance (MDR); Nonnucleoside reverse transcriptase inhibitor (NNRTI); Nucleoside reverse transcriptase inhibitor (NRTI); Resistance

Indexed keywords

1,3 DIOXOLANE DERIVATIVE; 2,6 DIAMINOPURINE DIOXOLANE; ABACAVIR; ADEFOVIR; ADENOSINE DEAMINASE; AMDOXOVIR; DIDANOSINE; DIOXOLANE GUANOSINE; EFAVIRENZ; EMTRICITABINE; LAMIVUDINE; NEVIRAPINE; NUCLEOSIDE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; UNCLASSIFIED DRUG; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; ARTICLE; CODON; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; GENE INSERTION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; VIRUS MUTATION; VIRUS RECOMBINANT; VIRUS TYPING;

EID: 0036156325     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/00042560-200201010-00002     Document Type: Article

References (45)

1. Design, activity, and 2.8 angstrom crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease
2. Rational design of peptide-based HIV proteinase inhibitors
3. Preclinical evaluation of MKC442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro
4. Effects of non-nucleoside inhibitors of human immunodeficiency virus type 1 in cell-free recombinant reverse transcriptase
5. The structure of HIV-1 reverse transcriptase
6. Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors
7. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors
8. A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site
9. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′triphosphate with human immunodeficiency virus reverse transcriptase
10. Effects of (-)-2′-deoxy-3′-thiacytidine (3TC) 5′-triphosphate on human immunodeficiency virus reverse transcriptase and mammalian DNA polymerases alpha, beta, and gamma
11. Inhibition of in vitro infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2′, 3′-dideoxynucleoside
12. 3′-Azido-3′-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase
13. Clinical pharmacology of 3′-azido-2′,3′-dideoxythymidine (zidovudine) and related dideoxynucleosides
14. Strategies for rescue therapy
15. Strategies for long-term success in the treatment of HIV infection
16. Viral dynamics in human immunodeficiency virus type 1 infection
17. Treatment of HIV disease in the new millennium
18. The picture of future therapy
19. Mechanism of action of 1-β-D-2,6-diaminopurine dioxolane: A prodrug of the HIV-1 inhibitor 1-β-D-dioxolane guanosine
20. Mechanism of action and in vitro activity of 1′,3′-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants
21. New soluble formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity
22. A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant HIV-1 isolates from patients treated with antiretroviral drugs
23. Comprehensive HIV drug resistance monitoring using rapid, high-throughput phenotypic and genotypic assays with correlative data analysis
24. Rapid and sensitive viral culture method for human immunodeficiency virus type 1
25. Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates
26. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase
27. In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-β-D-dioxolaneguanosine and suppress resistance to 3′-azido-3′-deoxythymidine
28. Resistance to DDI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase
29. 3′-Azido-3′-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors
30. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT)
31. Zidovudine-resistant human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine
32. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy
33. Resistance of clinical isolates of human immunodeficiency virus to antiretroviral agents
34. Abacavir and mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, have profound and synergistic HIV activity
35. Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy
36. Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2′,3′-dideoxynucleoside 5′-triphosphates
37. A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2′,3′ 2′,3′-dideoxy-3′-thiacytidine
38. Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain
39. Multidrug resistant genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: Incidence and association with other resistance mutations
40. A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors
41. The K65R mutation in HIV-1 reverse transcriptase causes resistance to (-)-β-D-dioxolane guanine and reverses AZT resistance
42. Preliminary assessments of the pharmacokinetics of DAPD and its active metabolite DXTG in HIV-infected subjects
43. Prevalence of mutations associated with reduced antiretroviral drug susceptibility among human immunodeficiency virus type 1 seroconverters in the United States, 1993-1998
44. Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure
45. Anti-HIV activity of DAPD in treatment-naive and treatment-experienced subjects