Influenza virus-IN-6 (Compound 35) serves as a potent inhibitor targeting the N-terminal domain of the polymerase acidic protein (PA N ) endonuclease subunit of the influenza virus, exhibiting an inhibitory concentration 50 (IC 50 ) value of 0.20 μM [1].

Influenza virus-IN-6 (Compound 35) exhibits anti-influenza virus activity with EC50 values of 1.28 ± 0.35, 1.12 ± 0.65, 0.76 ± 0.11, and 0.43 ± 0.06 μM against H1N1, H5N1, H3N2, and Flu B, respectively, in MDCK cells after 48 hours [1]. The compound, at concentrations of 5-20 μM for 24 hours, affects viral replication but does not impact viral particles, cellular adsorption, or release [1]. At 2.5-10 μM for 24 hours, Influenza virus-IN-6 inhibits the activity of the influenza virus polymerase [1]. Additionally, the compound demonstrates good stability in mouse plasma, liver microsomes, and intestinal S9-UDPGA [1].

Influenza virus-IN-6 (Compound 35) administered intraperitoneally at a dosage of 7.5-30 mg/kg/d twice daily for seven days significantly protected mice against influenza virus infection [1]. The in vivo pharmacokinetic (PK) profile of Influenza virus-IN-6 (Compound 35) following a single dose in rats (n = 5) revealed the following parameters: for intravenous (IV) administration (2 mg/kg), the half-life (T 1/2) was 0.33 ± 0.07 hours; for oral (PO) administration (10 mg/kg), T 1/2 was 0.82 ± 0.16 hours and time to maximum concentration (T max) was 0.52 hours; for intraperitoneal (IP) injection (15 mg/kg), T 1/2 was 1.07 ± 0.25 hours, and T max was 0.45 hours. Peak plasma concentration (C max) was 1586.55 ± 366.48 ng/mL (IV), 92.20 ± 36.25 ng/mL (PO), and 889.52 ± 233.17 ng/mL (IP). The area under the curve (AUC 0-t) was 536.45 ± 58.72 h·ng/mL (IV), 164.30 ± 26.37 h·ng/mL (PO), and 790.62 ± 188.31 h·ng/mL (IP). Clearance (CL) was measured at 53.76 ± 13.18 mL/min/kg (IV), and bioavailability (F %) was determined to be 6.13% (PO) and 29.50% (IP) [1]. IV represents intravenous injection, IP represents intraperitoneal injection, and PO represents the gastrointestinal route.