Pimodivir

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Pimodivir (VX-787、JNJ872、JNJ 63623872) 是一流的、口服生物可利用的流感病毒聚合酶 PB2 亚基抑制剂，Kd <3 nM，CPE EC50 为 2 nM。

Pimodivir (VX-787, JNJ872, JNJ 63623872) is a first-in-class, orally bioavailable inhibitor of influenza virus polymerase PB2 subunit with Kd of <3 nM, CPE EC50 of 2 nM; shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains with mean CPE EC50 of <2 nM; Pimodivir (VX-787) is highly efficacious in both prophylaxis and treatment models of mouse influenza and is superior to the neuraminidase inhibitor Oseltamivir.Influenza Phase 3 Clinical(In Vitro):Pimodivir rescues macrophages from virus-mediated death at non-cytotoxic concentrations 24 hpi. The EC50 value for Pimodivir are 8 and 12 nM for A(H1N1) and A(H3N2) strains, respectively, whereas the CC50 values are >1 μM, giving selectivity indexes (SI) > 125 and > 83 for A(H1N1) and A(H3N2) strains, respectively. Pimodivir significantly attenuates the transcription of viral M1 RNA in macrophages, which are infected with A(H1N1) or A(H3N2) strains for 8 h. Pimodivir inhibits the transcription of viral but not cellular genes. Pimodivir allows some activation of IAV-mediated expression of several cellular genes, which are involved in tryptophan and nucleotide metabolism. Pimodivir possesses excellent anti-IAV but not immuno/metabolo-modulating effect. Pimodivir (VX-787) is very potent against influenza A strains, including pandemic 2009 H1N1 and avian H5N1. Pimodivir (VX-787) shows potent activity against all influenza A virus strains tested, with an EC50 range of 0.13 to 3.2 nM. Pimodivir-selected PB2 variant viruses maintain susceptibility to neuraminidase inhibitors in vitro.(In Vivo):Pimodivir (2, 6, and 20 mg/kg/day, p.o.) and GS 4071 (20 mg/kg/day) completely prevent death in the H1N1pdm virus infection in mice. Pimodivir (20 mg/kg/day) is more effective than GS 4071 (20 mg/kg/day) in improving body weight and reducing the severity of lung infection. Moreover, Pimodivir (VX-787) shows 100% survival in a +48 h delay to treatment mouse influenza model at 10, 3 and 1 mpk (BID × 10 days) whereas the SOC, GS 4071, provide no survival benefit in this model at 10 mpk. Pimodivir (VX-787; 1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice.

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VX-787 | JNJ872 | JNJ 63623872

Microbiology/Virology

Influenza Virus

InfluenzaApolymerases

Infection

Influenza

1629869-44-8

399.394

C20H19F2N5O2

>98% (HPLC)

DMSO: ≥ 12.5 mg/mL

O=C([C@H]1C(CC2)CCC2[C@@H]1NC3=NC(C4=CNC5=NC=C(F)C=C54)=NC=C3F)O

Bicyclo[2.2.2]octane-2-carboxylic acid, 3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-pyrimidinyl]amino]-, (2S,3S)-

(-20℃)

With Ice Pack

≥ 2 years