NNRTIs-IN-1 is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) with notable anti-resistance efficacy, effectively inhibiting both the wild-type HIV-1 and five mutant strains at EC50 values within the nanomolar range. This compound also exhibits favorable pharmacokinetic properties [1].

NNRTIs-IN-1 (compound 8r) inhibits wild-type HIV-1 (EC50 = 2.3 nM) and five mutant strains: K103N (EC50 = 8 nM), E138K (EC50 = 6 nM), L100I (EC50 = 13 nM), Y181C (EC50 = 29 nM), and Y188L (EC50 = 52 nM) [1]. Additionally, NNRTIs-IN-1 lacks significant inhibitory activity against CYP1A2, CYP2D6, CYP3A4-T, and CYP3A4-M with IC50 values exceeding 50 μM, and it exhibits very weak activity against RPV-sensitive CYP2C9 and CYP2C19 isoforms (IC50 = 18.5 and 23.6 μM) [1]. Furthermore, NNRTIs-IN-1 shows minimal inhibition of hERG (IC50 > 40 μM) [1].

NNRTIs-IN-1 (compound 8r) administered intravenously (i.v.) at a dosage of 1 mg/kg displayed a half-life of 3.66 hours and a mean residence time (MRT) of 3.75 hours, with a peak concentration (Cmax) reaching 431 ng/mL [1]. At the same dosage, NNRTIs-IN-1 delivered i.v. had a half-life of 5.18 hours, an MRT of 5.21 hours, and a Cmax of 616 ng/mL, with an oral bioavailability (F) of 31.19% [1]. Furthermore, NNRTIs-IN-1 exhibited good tolerability when administered orally (p.o.) at a dose of 2 g/kg [1].