RU.521
(Synonyms: RU320521) 目录号 : GC37570
RU.521 （RU320521）是一种有效的选择性环状GMP-AMP合酶 （cGAS）抑制剂，可与cGAS 的催化结构域结合，从而抑制dsDNA对cGAS的激活，RU.521抑制cGAS介导的信号传导的IC50值为700nM。
Cas No.:2262452-06-0
Sample solution is provided at 25 µL, 10mM.
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RU.521 (RU320521) is a potent and selective cyclic GMP-AMP synthase (cGAS) inhibitor that binds to the catalytic domain of cGAS, thereby inhibiting the activation of cGAS by dsDNA. The IC50 value of RU.521 in inhibiting cGAS-mediated signal transduction is 700nM[1].
RU.521 (10μM) can inhibit the replication of human metapneumovirus (hMPV) in 16HBE cells, and exogenous addition of interleukin 1 beta (IL-1β) in the presence of RU.521 does not affect hMPV replication (IL-1β can promote hMPV replication) [2]. RU.521 (700nM) can reverse the damage of HUVEC cells caused by neutrophil extracellular traps (NETs) by inhibiting the cGAS/STING pathway[3].
RU.521 (5mg/kg) can inhibit the cGAS-STING pathway and reduce endoplasmic reticulum stress (ERS), thereby alleviating lung injury and promoting pulmonary ventilation function in rats with pulmonary ischemia/reperfusion (I/R)[4]. Intracisternary infusion of RU.521 (0.4mg/kg) in hypertensive mice reduced the expression of cGAS and STING in the paraventricular nucleus (PVN) of mice, and also reduced the LC3II/I ratio and p62 expression level[5].
References:
[1] Vincent J, Adura C, Gao P, Luz A, Lama L, Asano Y, Okamoto R, Imaeda T, Aida J, Rothamel K, Gogakos T, Steinberg J, Reasoner S, Aso K, Tuschl T, Patel DJ, Glickman JF, Ascano M. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun. 2017 Sep 29;8(1):750. doi: 10.1038/s41467-017-00833-9. Erratum in: Nat Commun. 2017 Nov 23;8(1):1827.
[2] Wu G, Zhang Y, Niu L, Hu Y, Yang Y, Zhao Y. Interleukin-1β promotes human metapneumovirus replication via activating the cGAS-STING pathway. Virus Res. 2024 May;343:199344.
[3] Zhang B, Fang Z, Lin Y, et al. RU. 521 protects against neutrophil extracellular traps-induced vascular endothelial injury by inhibiting cGAS/STING pathway[J]. ||| Bangladesh Journal of Pharmacology|||, 2024, 19(2): 59-64.
[4] Vincent J, Adura C, Gao P, Luz A, Lama L, Asano Y, Okamoto R, Imaeda T, Aida J, Rothamel K, Gogakos T, Steinberg J, Reasoner S, Aso K, Tuschl T, Patel DJ, Glickman JF, Ascano M. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun. 2017 Sep 29;8(1):750.
[5] Han C, Qian X, Ren X, Zhang S, Hu L, Li J, Huang Y, Huang R, Ooi K, Lin H, Xia C. Inhibition of cGAS in Paraventricular Nucleus Attenuates Hypertensive Heart Injury Via Regulating Microglial Autophagy. Mol Neurobiol. 2022 Nov;59(11):7006-7024.
RU.521 （RU320521）是一种有效的选择性环状GMP-AMP合酶 （cGAS）抑制剂，可与cGAS 的催化结构域结合，从而抑制dsDNA对cGAS的激活，RU.521抑制cGAS介导的信号传导的IC50值为700nM[1]。
RU.521（10μM ）可抑制16HBE细胞中的人偏肺病毒（hMPV）的复制，并且在RU.521存在下外源添加白细胞介素1 β（IL-1β）不会影响hMPV复制（IL-1β可促进hMPV复制）[2] 。RU.521（700nM）可通过抑制cGAS/STING通路，逆转中性粒细胞胞外陷阱（NETs）导致的HUVEC细胞的损伤[3] 。
RU.521（5mg/kg）可抑制cGAS-STING通路减弱内质网应激（ERS），从而减轻肺缺血/再灌注（I/R）大鼠的肺损伤并促进肺通气功能[4] 。在高血压小鼠脑池内输注RU.521（0.4mg/kg）降低了小鼠室旁核（PVN）中cGAS和STING的表达，也降低了LC3II/I比率和p62表达水平[5]。
| Cell experiment [1]: | |
Cell lines | 16HBE cells |
Preparation Method | 16HBE cells were pretreated with 1, 10 and 20μM of the cGAS inhibitor RU.521 for 24h, and then infected with Human metapneumovirus (hMPV) for 48h. |
Reaction Conditions | 1, 10 and 20μM, 24h |
Applications | HMPV replication decreased significantly after 16HBE cells were treated with different concentrations of inhibitors, and 10μM RU.521 had a significant inhibitory effect. |
| Animal experiment [2]: | |
Animal models | Lung ischemia/reperfusion（I/R）Sprague-Dawley rats model |
Preparation Method | Sprague-Dawley rats were subjected to left hilar occlusion reperfusion surgery to establish a pulmonary I/R model. Rats were intraperitoneally administered with cGAS-specific inhibitor RU.521, STING agonist SR-717, and ERS inhibitor 4-phenylbutyric acid (4-PBA). |
Dosage form | 5mg/kg, 1h, i.p. |
Applications | RU.521 attenuates pulmonary ischemia/reperfusion injury by inhibiting the cGAS-STING pathway. |
References: [1] Wu G, Zhang Y, Niu L, Hu Y, Yang Y, Zhao Y. Interleukin-1β promotes human metapneumovirus replication via activating the cGAS-STING pathway. Virus Res. 2024 May;343:199344. [2] Vincent J, Adura C, Gao P, Luz A, Lama L, Asano Y, Okamoto R, Imaeda T, Aida J, Rothamel K, Gogakos T, Steinberg J, Reasoner S, Aso K, Tuschl T, Patel DJ, Glickman JF, Ascano M. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun. 2017 Sep 29;8(1):750. | |
| Cas No. | 2262452-06-0 | SDF | |
| 别名 | RU320521 | ||
| Canonical SMILES | O=C1OC(C2=C(O)N(C3=NC4=CC=C(Cl)C(Cl)=C4N3)N=C2C)C5=C1C=CC=C5 | ||
| 分子式 | C19H12Cl2N4O3 | 分子量 | 415.23 |
| 溶解度 | DMSO: ≥ 125 mg/mL (301.04 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 | 2.4083 mL | 12.0415 mL | 24.083 mL |
| 5 mM | 0.4817 mL | 2.4083 mL | 4.8166 mL |
| 10 mM | 0.2408 mL | 1.2042 mL | 2.4083 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet