IR415
目录号 : GC61455IR415是有效的抗HBV试剂(anti-HBVagent),可通过阻断HBx的活性来抑制HBV复制。IR415选择性地与HBx相互作用(Kd=2nM)并阻断HBV介导的RNAi抑制,逆转HBx蛋白对Dicer核糖核酸内切酶活性的抑制作用。
Cas No.:452967-14-5
Sample solution is provided at 25 µL, 10mM.
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IR415 is a potent anti-HBV agent and inhibits HBV replication by blocking the HBx activity. IR415 selectively interacts with HBx (Kd=2 nM) and blocks HBV-mediated RNAi suppression, reverses the inhibitory effect of HBx protein on the activity of the dicer endoribonuclease[1]. HBx: hepatitis B virus X protein.
Hepatitis B virus X protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes[1].IR415 (50-200 μM) has a dose-dependent inhibitory effect on HBx, with a minimal effective concentration of 50 μM in HepG2/GFP-shRNA line transfected with HBx[1].
[1]. Ghosh S, et al. An RNAi-based high-throughput screening assay to identify small molecule inhibitors of hepatitis B virus replication.J Biol Chem. 2017 Jul 28;292(30):12577-12588.
Cas No. | 452967-14-5 | SDF | |
Canonical SMILES | S=C(NCCCN1C=CN=C1)NC2=CC=C(F)C=C2F | ||
分子式 | C13H14F2N4S | 分子量 | 296.34 |
溶解度 | DMSO: 125 mg/mL (421.81 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.3745 mL | 16.8725 mL | 33.745 mL |
5 mM | 0.6749 mL | 3.3745 mL | 6.749 mL |
10 mM | 0.3375 mL | 1.6873 mL | 3.3745 mL |
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2.
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An RNAi-based high-throughput screening assay to identify small molecule inhibitors of hepatitis B virus replication
J Biol Chem 2017 Jul 28;292(30):12577-12588.PMID:28584057DOI:PMC5535032
Persistent or chronic infection with the hepatitis B virus (HBV) represents one of the most common viral diseases in humans. The hepatitis B virus deploys the hepatitis B virus X protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes. Because of its critical role in countering host defenses, HBx represents an attractive target for antiviral drugs. Here, we developed and optimized a loss-of-function screening procedure, which identified a potential pharmacophore that abrogated HBx RNAi suppression activity. In a survey of 14,400 compounds in the Maybridge Screening Collection, we prioritized candidate compounds via high-throughput screening based on reversal of green fluorescent protein (GFP)-reported, RNAi-mediated silencing in a HepG2/GFP-shRNA RNAi sensor line. The screening yielded a pharmacologically active compound, N-(2,4-difluorophenyl)-N'-[3-(1H-imidazol-1-yl) propyl] thiourea (IR415), which blocked HBx-mediated RNAi suppression indicated by the GFP reporter assay. We also found that IR415 reversed the inhibitory effect of HBx protein on activity of the Dicer endoribonuclease. We further confirmed the results of the primary screen in IR415-treated, HBV-infected HepG2 cells, which exhibited a marked depletion of HBV core protein synthesis and down-regulation of pre-genomic HBV RNA. Using a molecular interaction analysis system, we confirmed that IR415 selectively targets HBx in a concentration-dependent manner. The screening assay presented here allows rapid and improved detection of small-molecule inhibitors of HBx and related viral proteins. The assay may therefore potentiate the development of next-generation RNAi pathway-based therapeutics and promises to accelerate our search for novel and effective drugs in antiviral research.