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

Abstract 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 (EC 50 ) 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 EC 50 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.