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ML303 Sale

目录号 : GC65122

ML303 是一种吡唑并吡啶类化合物, 是流感病毒非结构蛋白 1 (NS1) 的拮抗剂 (IC90 为 155 nM),其对流感病毒H1N1亚型的 EC50 值为0.7 μM。

ML303 Chemical Structure

Cas No.:1638211-04-7

规格 价格 库存 购买数量
1mg
¥2,070.00
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Sample solution is provided at 25 µL, 10mM.

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产品描述

ML303 is a pyrazolopyridine influenza virus nonstructural protein 1 (NS1) antagonist (IC90 = 155 nM), with an EC50 of 0.7 μM for Influenza A virus H1N1[1].

ML303 (20 μM, 6 h) treatment restore IFN-β mRNA levels in MDCK cells[1].

[1]. Patnaik S, et al. Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists. Bioorg Med Chem Lett. 2019 May 1;29(9):1113-1119.

Chemical Properties

Cas No. 1638211-04-7 SDF Download SDF
分子式 C21H16F3N3O2 分子量 399.37
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1 mM 2.5039 mL 12.5197 mL 25.0394 mL
5 mM 0.5008 mL 2.5039 mL 5.0079 mL
10 mM 0.2504 mL 1.252 mL 2.5039 mL
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Research Update

Discovery of Small Molecule Influenza Virus NS1 Antagonist

PMID:24260784DOI:NBK169451

The Non Structural 1 (NS1) is a 230–237 amino acid relatively well-conserved viral protein that is usually expressed only during infection [1]. It contains an RNA binding domain (RBD) and an effector domain (ED) that is connected by a variable linker [2]. The NS1 protein has been shown to be a key player that counters the host interferon (IFN) response to viral infection in strain-specific ways [3]. NS1 inhibits the function of OAS (2′–5′-oligoadenylate synthetase) and PKR (protein kinase R) [4] and block IFN-β synthesis at the post-transcriptional level by inhibiting the pre-mRNA splicing and blocking the export of poly(A)-RNAs from the nucleus to the cytoplasm [5]. It also hampers the host’s defense pathways by interfering with the host RNAi pathway, adaptive immune response, and the apoptotic response [6]. NS1 is also a key component in the temporal regulation of viral RNA synthesis, its splicing, and translation [7]. Thus, NS1 enhances the virulence of infection, posing as a compelling target for influenza treatment. These compounds will enable researchers to test how NS1 inhibition impacts the infection cycle and how antagonists can be leveraged alone or in combination with existing agents in the next generation of treatments for influenza infection. We developed and conducted a high-throughput screen using a novel yeast-based phenotypic assay to identify compounds which specifically inhibit NS1 function. Here we report a potent NS1 antagonist chemical series, represented by ML303. The SAR (structure activity relationship) around this chemical series was further developed by measuring the compound’s ability to inhibit replication of the influenza A/PR/8/34 virus in MDCK cells. The ML303 compound series specifically restored the NS1-inhibited expression of the interferon mRNA, inhibited the NS1 function in mechanistic assay and exhibited a potent antiviral activity in culture.