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GS-9620

现货
Catalog No.
A3444
TLR-7激动剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,200.00
现货
5mg
¥ 1,080.00
现货
10mg
¥ 1,800.00
现货
50mg
¥ 7,000.00
现货

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Background

GS-9620 is an orally active TLR7 agonist with EC50 of 291 nM. [1]
Toll-like receptor 7 (TLR7) is a pathogen recognition receptor which plays an important role in the detection of, and the innate immune response to, pathogens. TLR7 signaling is predominantly activated by viral single-stranded RNA and is localized within the endolysosomal compartments of plasmacytoid dendritic cells (pDCs) and B lymphocytes in humans and non-human primates. Activation of pDCs plays an important role in the progress of innate response to viral pathogens and are involved in the majority of type I interferon (IFN) production during the acute phase of an infection by viruses. The induction and secretion of endogenous IFNs, including IFN-α and IFN- β, also induce the development of an efficient adaptive immunological response. Interferons induce the transcription of interferon-stimulated genes (ISGs) which generate an antiviral state within cells, as well as induce the production of other cytokines and chemokines which facilitate intercellular communication and cellular trafficking. GS-9620 could activate TLR7 signaling in immune cells to induce clearance of virus infected cells. [1, 2]
GS-9620 selectively induces IFN-α, cytokines and chemokines. The minimum effective concentrations for IFN-α induction were similar in pDCs and in PBMCs from HCV-positive donors. GS-9620 demonstrates an EC50 of 291 nM for human TLR7, which is 30-fold selectivity over TLR8 with EC50 of 9 μM. [1]
GS-9620 was administered to HBV infected chimpanzees for 8 weeks with an interval of 1 week. Consequently, serum concentrations of HBV surface antigen and HBV antigen, and the number of HBV antigen–positive hepatocytes, were decreased as hepatocyte apoptosis increased. In a phase 1 clinical trial to evaluate the safety and tolerability of GS-9620, treatment of GS-9620 results in dose dependent increases in select cytokines, chemokines, and ISGs beginning at 2mg and is safe in a single dose up to 12mg. Increases in percentages of immunocytes, like T cells, B cells and NK cells, expressing CD69 were also noted in subjects receiving GS-9620 treatment. [2, 3]
References:
[1]. Turnas P, Zheng X, Lu B, et al. 1129 Preclinical characterization of GS-9620, a potent and selective oral TLR7 agonist[J]. Journal of Hepatology, 2011, 54: S446-S447.
[2]. Lanford R E, Guerra B, Chavez D, et al. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees[J]. Gastroenterology, 2013, 144(7): 1508-1517. e10.
[3]. Lopatin U, Wolfgang G, Kimberlin R, et al. 737 A phase-i, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single escalating oral doses of GS-9620 in healthy subjects[J]. Journal of Hepatology, 2011, 54: S296.

Chemical Properties

StorageStore at -20°C
M.Wt410.51
Cas No.1228585-88-3
FormulaC22H30N6O2
SynonymsGS 9620;GS9620
Solubility≥20.55 mg/mL in DMSO, ≥9.9 mg/mL in EtOH with ultrasonic and warming, <2.66 mg/mL in H2O
Chemical Name4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one
SDFDownload SDF
Canonical SMILESCCCCOC1=NC2=C(C(=N1)N)NC(=O)CN2CC3=CC(=CC=C3)CN4CCCC4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

外周血单核细胞(PBMC)或浆细胞样树突状细胞(pDC)

制备方法

溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

14 ~ 66 nM

实验结果

在人与食蟹猴PBMC和/或pDC中,GS-9620诱导干扰素 (IFN)-α和其它细胞因子,其最小有效浓度为14 ~ 66 nM。GS-9620对猴子的作用比对人的作用少5倍。

动物实验 [1]:

动物模型

食蟹猴

给药剂量

0.1 ~ 2.0 mg(单剂量),0.1 ~ 1.0 mg(每日1次,持续7天)或0.05 ~ 1.5 mg(每2日1次,持续28天);口服给药

实验结果

在最高口服剂量下,食蟹猴对GS-9620的耐受性良好(1.5 mg,每2日1次,持续28天)。GS-9620呈剂量依赖性地增加IFN-α、免疫调节细胞因子、趋化因子以及外周血细胞IFN激活基因(ISG)。此外,隔日给药没有造成快速耐受。虽然口服给药使全身生物利用度受限,但具有较高的口服吸收。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Turnas P, Zheng X, Lu B, et al. 1129 Preclinical characterization of GS-9620, a potent and selective oral TLR7 agonist[J]. Journal of Hepatology, 2011, 54: S446-S447.

生物活性

Description GS-9620是一种可口服的Toll样受体7 (TLR-7)的高效选择性小分子激动剂。
靶点 TLR-7          
IC50            

质量控制

化学结构

GS-9620