FIG 1.
CX14442 and GS-9822 block HIV-1-induced cell toxicity and inhibit the interaction between HIV-1 integrase and LEDGF/p75. (a and d) Chemical structures of CX14442 and GS-9822. (b and e) Dose-response curves for MTT viability assays with CX14442 and GS-9822 in MT4-cells 5 days after infection with HIV-1 (strain IIIB). Cell viability, measured as optical density (OD) values, is greatly reduced upon HIV-1 infection but increases upon addition of the compounds. Results are plotted as a percentage of the OD values obtained in uninfected, untreated cells within the same experiment. Mean values and standard deviations (SD) are shown for CX14442 (n = 4) and GS-9822 (n = 5). Each sample was run in triplicate. (c and f) Dose-response curves of CX14442 and GS-9822 in AlphaScreen. Increasing concentrations of compound were added to 50 nM HIV-1 integrase (strain NL4.3) and 100 nM LEDGF/p75. Data shown are mean values and standard deviations for 3 experiments, with each analysis performed in duplicate. Data are plotted as a percentage of the signal in the no-drug control.