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。

AVG-233 is a potent, orally active RNA 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 L 1-1749 fragment. AVG-233 has nanomolar activity against both RSV strains and clinical RSV isolates ( EC 50 =0.14-0.31 μM). AVG-233 can be used for research of respiratory syncytial virus (RSV) [1] [2].

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 (EC 50 =0.31 μM), RSV strain 2-20 (EC 50 =0.14 μM) and RSV clinical isolate 718 (EC 50 =0.2 μM) [1]. AVG-233 (1.25-40 μM; 0-300 s) suppresses RNA synthesis by the L 1-1749 fragment in a dose-dependent manner with an IC 50 value of 13.7 μM. AVG-233 bounds L and the L 1-1749 fragment with similar affinities (dissociation constants (KD’s) are 38.3 μM and 53.1 μM, respectively) [2].

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 log 10 TCID 50 (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 T max C max AUC 0-∞ CL/F T 1/2 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

2151937-80-1

C26H22ClN5O3

487.94

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years