| Bioactivity | JNJ4796 is an oral active fusion inhibitor of influenza virus, neutralizing influenza A group 1 viruses by inhibiting hemagglutinin (HA)-mediated fusion. JNJ4796 mimics the functionality of the broadly neutralizing antibodies (bnAbs)[1]. | ||||||||||||
| Target | EC50: 12 nM (H1/Bris), 66 nM (H1/Cal), 38 nM (H1/NCa), 22 nM (H1/PR8), 13 nM (H1/SI06), 449 nM (H5/H97), 3.24 μM (H5/Viet).Hemagglutinin. | ||||||||||||
| Invitro | Like bnAb CR6261, the mechanism of action of JNJ4796 is demonstrated to be based on inhibition of the pH-sensitive conformational change of HA that triggers fusion of the viral and endosomal membranes and release of the viral genome into the host cell[1]. | ||||||||||||
| In Vivo | Oral administration of JNJ4796 protects mice from lethal challenge of 25 times the median lethal dose (LD50) of H1N1 A/Puerto Rico/8/1934 virus. Doses of 50 and 10 mg/kg of JNJ4796 twice daily, initiated one day before challenge and continuing for 7 days, results in 100% survival at day 21 in comparison to the less potent compound JNJ8897 for which less than 50% survival is achieved[1].Oral doses of JNJ4796 results in dose-dependent efficacy after a sublethal viral challenge (LD90), with twice daily administration of 15 and 5 mg/kg of JNJ4796 giving rise to 100% survival[1]. Animal Model: | ||||||||||||
| Name | JNJ4796 | ||||||||||||
| CAS | 2241664-16-2 | ||||||||||||
| Formula | C28H27N9O3 | ||||||||||||
| Molar Mass | 537.57 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. van Dongen MJP, et al. A small-molecule fusion inhibitor of influenza virus is orally active in mice. Science. 2019 Mar 8;363(6431). |