AVG-233 是一种口服有效的 RNA 依赖性 RNA 聚合酶 (RdRp) 抑制剂。AVG-233 阻止启动子上的病毒聚合酶复合物的启动。AVG-233 结合位点存在于 L1-1749片段中。AVG-233 对 RSV 毒株和临床分离株均具有纳摩尔活性 (EC50=0.14-0.31 μM)。AVG-233 可用于呼吸道合胞病毒 (RSV) 研究。
| 生物活性 | AVG-233 is a potent, orally activeRNA dependent RNA polymerase (RdRp)inhibitor. AVG-233 prevents initiation of the viral polymerase complex at the promoter. AVG-233 binding site is present in the L1-1749fragment. AVG-233 has nanomolar activity against bothRSVstrains and clinicalRSVisolates (EC50=0.14-0.31 μM). AVG-233 can be used for research of respiratory syncytial virus (RSV)[1][2]. |
体外研究
(In Vitro) | AVG-233 (1-100 μM) blocks 3'RNA extension elongation but does not interfere with 3'RNA extension by up to three nucleotides after de novo initiation from the promoter or back-priming[1].
AVG-233 (20 μM) reduces virus yield of RSV A2-L19F (EC50=0.31 μM), RSV strain 2-20 (EC50=0.14 μM) and RSV clinical isolate 718 (EC50=0.2 μM)[1].
AVG-233 (1.25-40 μM; 0-300 s) suppresses RNA synthesis by the L1-1749fragment in a dose-dependent manner with an IC50value of 13.7 μM. AVG-233 bounds L and the L1-1749fragment with similar affinities (dissociation constants (KD’s) are 38.3 μM and 53.1 μM, respectively)[2].
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体内研究
(In Vivo) | AVG-233 (50-100 mg/kg; i.g.; once) decreases lung viral load in the RSV mouse model[2].
AVG-233 (2-20 mg/kg; i.v. and p.o.; once; male CD-1 mice) has good orally bioavailable and the maximum plasma concentration about 2 μM[1].
| Animal Model: | Female Balb/cJ mice with recRSV-mKate xenograft[2] | | Dosage: | 50 and 100 mg/kg | | Administration: | Oral gavage; once | | Result: | Reduced in lung viral load of 0.89 log10TCID50(median tissue culture infectious dose)/mL. |
| Animal Model: | Male CD-1 mice (27-29 g)[1] | | Dosage: | 2 mg/kg (i.v.) and 20 mg/kg (p.o.) | | Administration: | Intravenous injection and oral administration; once, obtains blood samples at pre-dose and 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 h post-dosing | | Result: | 1.19|
| Route | Dose | Tmax | Cmax | AUC0-∞ | CL/F | T1/2 | Bioavailability | | mg/kg | h | nmol/ml | h×nmol/ml | liters/h/kg | h | % | | Oral | 20 | 1 | 2.17 | 5.95 | 6.98 | 5.28 | 33.8 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
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