NNRT-IN-10 is a potent, selective, and orally bioavailable non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV-1. The compound exhibits EC50 values ranging from 1.16 to 18.3 nM against HIV and its variants. NNRT-IN-10 has favorable pharmacokinetic properties and safety profile, making it suitable for research on AIDS caused by HIV-1.

HIV-1 (WT):1.16 nM (EC50)

NNRT-IN-10 (Compound 5i3) demonstrates improved resistance profiles and negligible cytotoxicity, with EC 50 values of 1.16 nM for HIV-1 (WT), 2.64 nM for P1579, 12.5 nM for P5375, 3.70 nM for P1833, and 18.3 nM for P5735. In MT-4 cells over five days, NNRT-IN-10 effectively inhibits HIV-1 IIIB replication at nanomolar levels (EC 50 = 1.4 nM). It exhibits weak inhibition against cytochrome P450 enzymes: CYP1A2 (IC 50 = 56.6 μM), CYP2C9 (IC 50 = 6.76 μM), CYP2C19 (IC 50 = 8.47 μM), and CYP2D6 (IC 50 = 12.7 μM). Additionally, NNRT-IN-10 demonstrates potassium channel inhibitory activity in CHO-hERG cells (0.3-40 μM, 24 h), with an IC 50 of 1.48 μM.

NNRT-IN-10 (Compound 5i3) is well-tolerated at a single oral dose of 800 mg/kg, exhibiting no acute toxicity in mice.