Disease relevance of AIDS-010086

• Suppression of HIV expression by WR-151327 was observed in the absence of a cytotoxic or cytostatic effect [1].
• WR-151327 increases resistance to Klebsiella pneumoniae infection in mixed-field- and gamma-photon-irradiated mice [2].
• In addition, WR-151327 suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD) [1].
• PURPOSE: To determine the efficacy of WR-151327 (WR) [S-3-(3-methylaminopropylamino) propylphosphorothioic acid; (CH3-HN-(CH2)3-NH-(CH2)3-S-PO3H2)] in increasing resistance to bacterial infection after a sublethal dose of gamma-photons or mixed-field neutrons plus gamma-photons [2].
• The calculated radioprotective dose reduction factors (DRF) at 450 mg per kg and 900 mg per kg of body weight (BW) WR-151327 were 1.2 and 1.3, respectfully [3].

High impact information on AIDS-010086

• Incubation of WR-151327 with human recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to induce the expression of HIV [1].
• We present data which show the effects of the organic thiophosphate WR-151327 on the expression of latent HIV in U1 cells [1].
• Histopathological effects of WR-151327 were restricted to the testes, salivary gland, and pancreas [4].
• Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice [5].
• Two thiophosphoroate radiation protectors (WR-2721 and WR-151327) were assessed for their ability to modify the effects of neutron or gamma irradiation on the gastrointestinal tract [6].

Anatomical context of AIDS-010086

• Moreover, there was a dramatic reduction in the germinal cells in mice seminiferous tubules treated with a combination of 450 mg per kg WR-151327 plus 10 Gy radiation after eight days [3].

Associations of AIDS-010086 with other chemical compounds

• In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD(10)) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and gamma-rays (n/gamma=1) or 60Co gamma-rays [7].

Analytical, diagnostic and therapeutic context of AIDS-010086

• Preclinical evaluation of WR-151327: an orally active chemotherapy protector [8].
• Pretreatment with WR-151327 also suppressed the induction of total HIV protein synthesis, as shown by Western blot analysis [1].
• There was a decrease in the number of cells in the germinal cell layers of testes from animals administered 450 mg per kg WR-151327 or 10 Gy whole body irradiation after eight days [3].
• This paper describes applications of sensitive and specific procedures such as capillary column gas chromatography with flame ionization detection, electron impact mass spectrometry and liquid chromatography with electrochemical detection for structural characterization and analysis of the active forms of WR-151327 [9].

References