Disease relevance of WHI-05

• The improved potency, as well as the lack of mucosal, systemic and reproductive toxicity of WHI-05 and WHI-07, means that these compounds have clinical potential as safe, prophylactic contraceptives in addition to their microbicide activity to curb the sexual transmission of HIV [1].
• WHI-05 inhibited the replication of ZDV-sensitive as well as ZDV-resistant strains of HIV in PBMC [2].

High impact information on WHI-05

• Repetitive intravaginal administration of 2% WHI-05 and WHI-07 via a gel-microemulsion to achieve concentrations as high as 6.1 x 10(4) and 5.7 x 10(6) times their respective in vitro anti-HIV IC50 values, and 1200 and 5700 times their spermicidal EC50 values, for up to 13 weeks, was not associated with mucosal, systemic or reproductive toxicity [1].
• We investigated the TK activity and intracellular metabolism of WHI-05 and WHI-07 in normal human vaginal and cervical epithelial cells as well as sperm [3].
• These results demonstrate that human female genital tract epithelial cells and sperm efficiently convert WHI-05 and WHI-07 to bioactive ZDV metabolites despite their TK deficiency [3].
• CASA combined with HR-LVSEM demonstrated that WHI-05-induced SIA was not associated with membrane damage [2].
• The anti-HIV activities of WHI-05 and ZDV were compared by measuring p24 antigen production and reverse transcriptase activity as markers of viral replication using human peripheral blood mononuclear cells (PBMC) infected with both ZDV-sensitive and ZDV-resistant strains of HIV [2].

Chemical compound and disease context of WHI-05

• Female cynomolgus monkeys treated with 20 mg/kg WHI-05 and WHI-07 intravenously developed no grade 2-4 systemic toxicities [1].

Biological context of WHI-05

• Exposure of semen to WHI-05 at the time of artificial insemination inhibited pregnancy and embryo implantation by 90% [4].

Anatomical context of WHI-05

• Repetitive intravaginal application of a 2% WHI-05 gel-microemulsion did not damage the vaginal epithelium or cause local inflammation in the rabbit model [2].

Associations of WHI-05 with other chemical compounds

• Thymidine kinase-independent intracellular delivery of bioactive nucleotides by aryl phosphate derivatives of bromo-methoxy zidovudine (compounds WHI-05 and WHI-07) in normal human female genital tract epithelial cells and sperm [3].
• The sperm immobilizing activity (SIA) of WHI-05 was compared with that of ZDV and nonoxynol-9 (N-9) by computer-assisted sperm analysis (CASA) [2].

Analytical, diagnostic and therapeutic context of WHI-05

• The effect of WHI-05 on sperm membrane integrity was examined by high resolution, low voltage scanning electron microscopy (HR-LVSEM) [2].

References