Neuraminidase-IN-11

Neuraminidase-IN-11 (15e) is a potent and selective neuraminidase (NA) inhibitor with the IC50 values of 4.7 nM, 8.46 nM and 1.5 nM against H1N1, H5N1 and H5N8 NAs respectively[1].

Signaling Pathways >> Anti-infection >> Influenza Virus

Research Areas >> Infection

Neuraminidase-IN-11 (15e) (0-6 μM, 40 min)has anti-NA (Neuraminidase) activity against H1N1-H274Y mutant and H5N1-H274Y mutant with the IC50 values of 1.07 μM and 0.61 μM, respectively[1]. Neuraminidase-IN-11 (15e) (0-20 μM, 48 h) inhibits chicken embryo fibroblasts (CEFs) infected H5N1 or H5N8 with the IC50 values of 4.4 μM and 0.57 μM respectively, and inhibits Madin−Darby canine kidney (MDCK) cells infected H1N1 or H3N2 with the IC50 values of 0.05 μM and 12.65 μM respectively[1]. Neuraminidase-IN-11 (15e) has no significant inhibitory effect on the major CYP enzymes which acts on CYP1A2, CYP2C9 and CYP2C19 with the IC50 values of 28.9 μM, 47.3 μM and 47.8 μM, respectively[1]. The metabolic stability parameters of Neuraminidase-IN-11 (15e) in human liver microsomes (HLM)[1]. Parameters Neuraminidase-IN-11 (15e) t1/2 (min) >145 CLint(mic) (μL/min/kg) <9.6 CLint(liver) (mL/min/kg) <8.6 remaining (T = 60 min) (%) 79.3

Neuraminidase-IN-11 (15e) (oral administration, 50 mg/kg, every second day, 14 days) shows no significant change in body weight and no other toxic side effects in kunming mice[1]. Animal Model: Male Sprague−Dawley rat[1] Dosage: Administration: 2 mg/kg, i.v.; 20 mg/kg, p.o. Result: The pharmacokinetic parameters of Neuraminidase-IN-11 (15e) Parameters 15e (i.v.) 15e (p.o.) t1/2 (h) 0.213 0.863 Tmax (h) 0.083 0.5 Cmax (ng/mL) 7195 491 Vdss (mL/kg) 179 - CL 17.2 - F (%) - 1.58

[1]. Han Ju, et al. Iterative Optimization and Structure-Activity Relationship Studies of Oseltamivir Amino Derivatives as Potent and Selective Neuraminidase Inhibitors via Targeting 150-Cavity. J Med Chem. 2022 Aug 8.