ST-193
目录号 : GC37681
ST-193是有效广谱的arenavirus抑制剂；抑制Guanarito, Junin, Lassa和Machupo病毒的IC50值分别为0.44, 0.62, 1.4 和3.1 nM。
Cas No.:489416-12-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Guinea pigs: ST-193 is formulated as a solution in 32% (w/v) 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Female Hartley guinea pigs are injected intraperitoneally with a 10 mg/mL solution of ST-193 at a volume of either 2.5 mL per kg of body weight (25 mg/kg) or 10 mL per kg (100 mg/kg). Four animals per dose are used, with blood samples collected from two animals per dose at each time point in alternating fashion. Blood samples are obtained at the indicated time points (4-24 h)[3]. |
References: [1]. Burgeson JR, et al. Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles. Bioorg Med Chem Lett. 2013 Feb 1;23(3):750-6. | |
ST-193 is a potent broad-spectrum arenavirus inhibitor; inhibits Guanarito, Junin, Lassa and Machupo virus with IC50 values of 0.44, 0.62, 1.4 and 3.1 nM, respectively.
ST-193 inhibits LASV pseudotypes with an IC50 of 1.6 nM. ST-193 inhibits pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC50s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibits no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 μM[2].
ST-193 is found to be tolerated well when administered daily as an intraperitoneal injection of either 25 or 100 mg/kg/day for 14 days. ST-193-treated animals exhibit fewer signs of disease and enhance survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups are elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediates a 2- to 3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs is 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups[3].
References:
[1]. Burgeson JR, et al. Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles. Bioorg Med Chem Lett. 2013 Feb 1;23(3):750-6.
[2]. Larson RA, et al. Identification of a broad-spectrum arenavirus entry inhibitor. J Virol. 2008 Nov;82(21):10768-75.
[3]. Cashman KA, et al. Evaluation of Lassa antiviral compound ST-193 in a guinea pig model. Antiviral Res. 2011 Apr;90(1):70-9.
| Cas No. | 489416-12-8 | SDF | |
| Canonical SMILES | CC(C1=CC=C(CNC2=CC=C3C(N=CN3C4=CC=C(OC)C=C4)=C2)C=C1)C | ||
| 分子式 | C24H25N3O | 分子量 | 371.47 |
| 溶解度 | DMSO: ≥ 150 mg/mL (403.80 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.692 mL | 13.46 mL | 26.9201 mL |
| 5 mM | 0.5384 mL | 2.692 mL | 5.384 mL |
| 10 mM | 0.2692 mL | 1.346 mL | 2.692 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Evaluation of Lassa antiviral compound ST-193 in a guinea pig model
Antiviral Res 2011 Apr;90(1):70-9.PMID:21371508DOI:10.1016/j.antiviral.2011.02.012.
Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro. To determine the antiviral utility of ST-193 in vivo, we tested the efficacy of this compound in the LASV guinea pig model. Four groups of strain 13 guinea pigs were administered 25 or 80 mg/kg ST-193, 25 mg/kg of ribavirin, or the vehicle by the intraperitoneal (i.p.) route before infection with a lethal dose of LASV, strain Josiah, and continuing once daily for 14 days. Control animals exhibited severe disease, becoming moribund between days 10 and 15 postinfection. ST-193-treated animals exhibited fewer signs of disease and enhanced survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups were elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediated a 2-3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs was 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups. These data suggest that ST-193 may serve as an improved candidate for the treatment of Lassa fever.
Identification of a broad-spectrum arenavirus entry inhibitor
J Virol 2008 Nov;82(21):10768-75.PMID:18715909DOI:10.1128/JVI.00941-08.
Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral activity identified a modified structure, ST-193, with a 50% inhibitory concentration (IC(50)) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC(50)s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 microM. Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed mutagenesis. Taken together, these studies demonstrate that sensitivity to ST-193 is dictated by a segment of about 30 amino acids within the GP2 subunit. This region includes the carboxy-terminal region of the ectodomain and the predicted transmembrane domain of the envelope protein, revealing a novel antiviral target within the arenavirus envelope GP.
Screening Repurposed Antiviral Small Molecules as Antimycobacterial Compounds by a Lux-Based phoP Promoter-Reporter Platform
Antibiotics (Basel) 2022 Mar 9;11(3):369.PMID:35326832DOI:10.3390/antibiotics11030369.
The emergence of multidrug-resistant strains and hyper-virulent strains of Mycobacterium tuberculosis are big therapeutic challenges for tuberculosis (TB) control. Repurposing bioactive small-molecule compounds has recently become a new therapeutic approach against TB. This study aimed to identify novel anti-TB agents from a library of small-molecule compounds via a rapid screening system. A total of 320 small-molecule compounds were used to screen for their ability to suppress the expression of a key virulence gene, phop, of the M. tuberculosis complex using luminescence (lux)-based promoter-reporter platforms. The minimum inhibitory and bactericidal concentrations on drug-resistant M. tuberculosis and cytotoxicity to human macrophages were determined. RNA sequencing (RNA-seq) was conducted to determine the drug mechanisms of the selected compounds as novel antibiotics or anti-virulent agents against the M. tuberculosis complex. The results showed that six compounds displayed bactericidal activity against M. bovis BCG, of which Ebselen demonstrated the lowest cytotoxicity to macrophages and was considered as a potential antibiotic for TB. Another ten compounds did not inhibit the in vitro growth of the M. tuberculosis complex and six of them downregulated the expression of phoP/R significantly. Of these, ST-193 and ST-193 (hydrochloride) showed low cytotoxicity and were suggested to be potential anti-virulence agents for M. tuberculosis.
pH-induced activation of arenavirus membrane fusion is antagonized by small-molecule inhibitors
J Virol 2008 Nov;82(21):10932-9.PMID:18768973DOI:10.1128/JVI.01140-08.
The arenavirus envelope glycoprotein (GPC) mediates viral entry through pH-induced membrane fusion in the endosome. This crucial process in the viral life cycle can be specifically inhibited in the New World arenaviruses by the small-molecule compound ST-294. Here, we show that ST-294 interferes with GPC-mediated membrane fusion by targeting the interaction of the G2 fusion subunit with the stable signal peptide (SSP). We demonstrate that amino acid substitutions at lysine-33 of the Junín virus SSP confer resistance to ST-294 and engender de novo sensitivity to ST-161, a chemically distinct inhibitor of the Old World Lassa fever virus. These compounds, as well as a broadly active inhibitor, ST-193, likely share a molecular target at the SSP-G2 interface. We also show that both ST-294 and ST-193 inhibit pH-induced dissociation of the G1 receptor-binding subunit from GPC, a process concomitant with fusion activation. Interestingly, the inhibitory activity of these molecules can in some cases be overcome by further lowering the pH used for activation. Our results suggest that these small molecules act to stabilize the prefusion GPC complex against acidic pH. The pH-sensitive interaction between SSP and G2 in GPC represents a robust molecular target for the development of antiviral compounds for the treatment of arenavirus hemorrhagic fevers.
Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole
Bioorg Med Chem Lett 2013 Feb 1;23(3):744-9.PMID:23265895DOI:10.1016/j.bmcl.2012.11.095.
A chemically diverse library of about 400,000 small molecules was screened for antiviral activity against lentiviral pseudotypes with the Lassa virus envelope glycoprotein (LASV GP) gene incorporated. High-throughput screening resulted in discovery of a hit compound (ST-37) possessing a benzimidazole core which led to a potent compound series. Herein, we report SAR studies which involved structural modifications to the phenyl rings and methylamino linker portion attached to the benzimidazole core. Many analogs in this study possessed single digit nanomolar potency against LASV pseudotypes. Compounds in this benzimidazole series also exhibited nanomolar antiviral activity against pseudotypes generated from other arenavirus envelopes indicating the potential for development of a broad-spectrum inhibitor. Ultimately, lead compound ST-193 was identified and later found to be efficacious in a lethal LASV guinea pig model showing superior protection compared to ribavirin treatment.