Cabotegravir (S/GSK1265744) (GSK744, GSK1265744) is a long-acting HIV integrase inhibitor and inhibits the HIV-1 integrase catalyzed strand transfer reaction (IC50: 3.0 nM).

HIV-1:3.0 nM

GSK1265744 (50 mg/kg) effectively prevents high-dose SHIV infection in rhesus macaques.

In vitro strand transfer assay: The inhibitory concentrations of GSK1265744 is measured in a strand transfer assay using recombinant HIV IN. A complex of integrase and biotinylated donor DNA–streptavidin-coated SPA beads is formed by incubating 2 μM purified recombinant integrase with 0.66 μM biotinylated donor DNA–4 mg/mL streptavidin-coated SPA beads in 25 mM sodium MOPS pH 7.2, 23 mM NaCl, and 10 mM MgCl2 for 5 minutes at 37°C. These beads are spun down and preincubated with diluted INSTIs for 60 minutes at 37°C. Next, [3H]-labeled target DNA substrate is added to give a final concentration of 7 nM substrate, and the strand transfer reaction is incubated at 37°C for 25 to 45 minutes, which allowed for a linear increase in strand transfer of donor DNA to radiolabeled target DNA. The signal is read using a Wallac MicroBeta scintillation plate reader.

DMSO: 16.67 mg/mL (41.12 mM)

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)