HIV-1-IN-85 is an orally active HIV-1 inhibitor with an IC50 of 72 nM. It exhibits potent inhibitory activity against wild-type (WT) HIV-1 and single mutant strains resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as L100I, K103N, Y181C, Y188L, and E138K. Additionally, it shows moderate inhibitory activity against double mutant strains (F227L+V106A, RES056). In ICR mice, HIV-1-IN-85 demonstrates good in vivo safety and is suitable for research on HIV-1 infection.

HIV-1:72 nM

HIV-1-IN-85 (Compound (S)-5m) exhibits potent antiviral activity against wild-type (WT) HIV-1 and single mutant strains in MT-4 cells, with EC50 values of 3.7 nM (WT), 9.2 nM (L100I), 5.8 nM (K103N), 37 nM (Y181C), 231 nM (Y188L), 30 nM (E138K), 2399 nM (F227L+V106A), and 277 nM (RES056). In enzyme-level assays, it inhibits the polymerase activity of wild-type HIV-1 (IC50 = 72 nM). At a concentration of 40 μM for 24 hours, HIV-1-IN-85 minimally affects mitochondrial function in MT-4 cells and has negligible inhibition on the hERG channel.

Administered as a single oral dose of 2 g/kg, HIV-1-IN-85 (Compound (S)-5m) demonstrated favorable in vivo safety in ICR mice over a two-week observation period.