Pre-clinical pharmacological profile of QF-036, a potent HIV-1 maturation inhibitor

QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its Antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles were evaluated in rats and monkeys. The 50% effective concentrations (EC₅₀ ) of QF-036 against the three strains were 20.36 nM, 0.39 μM and 2.11 nM, respectively, demonstrating better Antiviral potential than the first-generation Antiviral maturation inhibitor bevirimat. QF-036 demonstrated moderate cell permeability, high plasma protein binding ability and good metabolic stability in vitro. After oral QF-036 administration to rats and monkeys, both species exhibited moderate bioavailability, and the plasma drug exposure increased in an approximately dose-proportional manner. When administered orally (30 mg/kg) to monkeys, the QF-036 plasma concentration (C_max ) peaked at 3671 ng/mL (4.82 μM), 12 to 2410 times higher than the EC50 of laboratory or resistant HIV-1 strains. Moreover, the plasma concentration of QF-036 at 12 hours after administration was 263 ng/mL (0.35 μM), which approximately matched the highest EC₅₀ value of the three test strains. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF-036 as a promising anti-HIV therapeutic candidate.

anti-HIV-1; bioavailability; drug metabolism; drug transport; pharmacokinetics.