ALS-8112是高效，选择性的呼吸道合胞病毒（RSV）聚合酶抑制剂。5'-三磷酸形式的ALS-8112抑制RSV聚合酶，IC50值为0.02μM。
CAS：1445379-92-9
分子式：C10H13ClFN3O4
分子量：293.68
纯度：98%
存储：Store at -20°C

Background:

ALS-8112 is a potent and selective respiratory syncytial virus (RSV) polymerase inhibitor. The 5’-triphosphate form of ALS-8112 inhibits RSV polymerase with an IC50 of 0.02 μM.

The 5’-triphosphate form of ALS-8112 (ALS-8112-TP) is the active form of the drug and selectively inhibits RSV polymerase through chain termination of RNA synthesis[2]. ALS-008112 enters various types of epithelial cells in the respiratory tract and is subsequently phosphorylated to form an intracellular nucleoside triphosphate with a half-life of approximately 29 hours. The nucleoside triphosphate analogue inhibits RSV replication by means of chain termination[3]. ALS-8112 is a pan-strain inhibitor of RSV replication in vitro. The RNA transcription activity of the RSV-RNP complex is dose-proportionally inhibited by ALS-8112-TP with an IC50 of 0.020 ± 0.008 μM[4].

[1]. Wang G, et al. Discovery of 4’-chloromethyl-2’-deoxy-3’,5’-di-O-isobutyryl-2’-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015 Feb 26;58(4):1862-78. [2]. Jordan PC, et al. Activation Pathway of a Nucleoside Analog Inhibiting Respiratory Syncytial Virus Polymerase. ACS Chem Biol. 2017 Jan 20;12(1):83-91. [3]. DeVincenzo JP, et al. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2015 Nov 19;373(21):2048-58. [4]. Deval J, et al. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2’-Fluoro-4’-Chloromethyl-Cytidine Triphosphate. PLoS Pathog. 2015 Jun 22;11(6):e1004995.