GS-9620 (Vesatolimod)是一种具口服活性的有效的Toll样受体7（TLR7）激动剂，EC50值为291nM，具有抗病毒作用。
Cas No.:1228585-88-3
Sample solution is provided at 25 µL, 10mM.
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GS-9620 (Vesatolimod) is a potent, orally active Toll-like receptor 7 (TLR7) agonist with an EC50 value of 291nM, exhibiting antiviral activity[1, 2]. TLR7 is a pathogen recognition receptor that plays a critical role in pathogen detection and in mediating innate immune responses against pathogens[3]. GS-9620 is capable of enhancing HIV-specific cytotoxicity and anti-HIV antibody-mediated immunity[4].
In vitro, treatment of peripheral blood mononuclear cells (PBMCs) with GS-9620 (10-1000nM) for 36h significantly increased cytokine levels in the culture supernatant; specifically, Interleukin-6 (IL-6) levels increased 218-fold, IFN-α increased 186-fold, and IFN-β increased 81-fold[5]. Treatment of FMDV-infected LFBK cells with GS-9620 (78-625μM) for 48 and 72h reduced intracellular viral copy numbers in a dose-dependent manner and elevated IFN-α levels in the cell supernatant[6].
In vivo, oral administration of GS-9620 (4.5mg/kg) three times to mice infected with the EV71 virus significantly alleviated clinical symptoms and improved survival rates. Furthermore, it significantly reduced serum levels of pro-inflammatory cytokines—such as IFN-α, IFN-γ, and MCP-1, and activated the NF-κB and PI3K/AKT signaling pathways within limb muscle cells[7].
References:
[1] Wang Y K, Wei L, Hu W, et al. Medicinal chemistry of anti-HIV-1 latency chemotherapeutics: biotargets, binding modes and structure-activity relationship investigation[J]. Molecules, 2022, 28(1): 3.
[2] Lopatin U, Wolfgang G, Tumas D, et al. Safety, pharmacokinetics and pharmacodynamics of GS-9620, an oral Toll-like receptor 7 agonist[J]. Antiviral therapy, 2013, 18(3): 409-418.
[3] Kawai T, Akira S. Pathogen recognition with Toll-like receptors[J]. Current opinion in immunology, 2005, 17(4): 338-344.
[4] Tsai A, Irrinki A, Kaur J, et al. Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy[J]. Journal of virology, 2017, 91(8): 10.1128/jvi. 02166-16.
[5] Bam R A, Hansen D, Irrinki A, et al. TLR7 agonist GS-9620 is a potent inhibitor of acute HIV-1 infection in human peripheral blood mononuclear cells[J]. Antimicrobial agents and chemotherapy, 2017, 61(1): 10.1128/aac. 01369-16.
[6] Lee G, Kang H R, Kim A, et al. Antiviral effect of vesatolimod (GS-9620) against foot-and-mouth disease virus both in vitro and in vivo[J]. Antiviral Research, 2022, 205: 105384.
[7] Zhang Q, Zhao B, Chen X, et al. GS-9620 inhibits enterovirus 71 replication mainly through the NF-κB and PI3K-AKT signaling pathways[J]. Antiviral Research, 2018, 153: 39-48.
GS-9620 (Vesatolimod)是一种具口服活性的有效的Toll样受体7（TLR7）激动剂，EC50值为291nM，具有抗病毒作用[1, 2]。TLR7是一种病原体识别受体，在检测病原体及对病原体的先天免疫反应中起着重要作用[3]。GS-9620能够增强HIV特异性细胞毒性和抗HIV抗体介导免疫[4]。
在体外，GS-9620（10-1000nM）处理外周血单核细胞（PBMCs）36h，显著增加了培养上清液中细胞因子水平，其中白细胞介素-6（IL-6）增加了218倍，IFN-α增加了186倍，IFN-β增加了81倍[5]。GS-9620（78-625μM）处理FMDV感染的LFBK细胞48h和72h，以剂量依赖性方式降低了细胞内病毒拷贝数，提高了细胞上清液中IFN-α水平[6]。
在体内，GS-9620（4.5mg/kg）通过口服治疗EV71病毒感染小鼠3次，显著缓解了小鼠的临床症状并提高了存活率，显著降低了血清中促炎细胞因子如 IFN-α、IFN-γ和MCP-1的水平，激活了肢体肌肉细胞中的NF-κB和PI3K/AKT信号通路[7]。
| Cell experiment [1]: | |
Cell lines | Peripheral blood mononuclear cells (PBMCs) |
Preparation Method | TLR7 agonist-induced cytokine levels observed in resting PBMCs at 36h posttreatment with GS-9620 (10 to 1000nM), imiquimod (0.5 to 10g/mL), or gardiquimod (0.1 to 2.5g/mL) versus those observed in PBMCs treated with DMSO, as determined by Luminex analysis of cell-free culture supernatants. |
Reaction Conditions | 10-1000nM; 36h |
Applications | Relative to the levels in DMSO-treated cultures, GS-9620-conditioned supernatants showed the greatest fold increase in interleukin-6 (IL-6; 218-fold), IFN-α (186-fold), and IFN-γ (81-fold) levels. |
| Animal experiment [2]: | |
Animal models | EV71-infected mice |
Preparation Method | Mice were orally administered a dose of 4.5mg/kg three times. The survival rates and clinical symptoms of the GS-9620-treated, EV71-infected mice were compared with those of untreated mice, and hind-limb muscle tissues were collected from the mice for subsequent analysis. |
Dosage form | 4.5mg/kg; p.o. |
Applications | GS-9620 treatment significantly increased the survival rates and ameliorated the clinical symptoms of EV71-infected mice. GS-9620 activated TLR7 in the limb muscle cells, which stimulated the NF-κB and PI3K/AKT signaling pathways. |
References: | |
| Cas No. | 1228585-88-3 | SDF | |
| 别名 | 维沙莫德; GS-9620 | ||
| 化学名 | 4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one | ||
| Canonical SMILES | CCCCOC1=NC2=C(C(=N1)N)NC(=O)CN2CC3=CC(=CC=C3)CN4CCCC4 | ||
| 分子式 | C22H30N6O2 | 分子量 | 410.51 |
| 溶解度 | ≥ 20.55 mg/mL in DMSO, ≥ 9.9 mg/mL in EtOH with ultrasonic and warming | 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 | 2.436 mL | 12.18 mL | 24.3599 mL |
| 5 mM | 487.2 μL | 2.436 mL | 4.872 mL |
| 10 mM | 243.6 μL | 1.218 mL | 2.436 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。
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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