CU CPT 4a
(Synonyms: TLR3-IN-1) 目录号 : GC11461CU CPT 4a 是一种有效的 Toll 样受体 3（TLR3）抑制剂，IC50值为3.44μM。
Cas No.:1279713-77-7
Sample solution is provided at 25 µL, 10mM.
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CU CPT 4a is a potent inhibitor of toll-like receptor 3 (TLR3), with an IC50 value of 3.44μM [1]. CU CPT 4a suppresses the downstream signaling pathways mediated by TLR3/dsRNA complex, resulting in inhibition of interferons and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) production[2]. CU CPT 4a has been widely used to regulate TLR3-mediated inflammation in animal models[3].
In vitro, CU CPT 4a pretreatment at 40μM for 1 hour significantly inhibited invasion of KKU213 cells induced by 2.5μg/ml Poly(I:C) (12h)[4]. CU CPT 4a treatment at 20µM for 1h significantly inhibited Tributyltin (TBT) (25nM)-induced IL-1β and IL-6 production in human peripheral blood mononuclear cells (PBMCs) [5]. CU CPT 4a treatment (10µM) for 24h abolished the stimulatory effect of histamine on TBK1/IRF3 signaling in SARS-CoV-2-infected Caco2 cells[6]. Treatment with 40μM CU CPT 4a for 24 hours reduced Caspase-3/7 activation without attenuating LPS-stimulated apoptosis in mouse cardiomyocytes[7].
In vivo, CU CPT 4a treatment via intraperitoneally injection (30μg/10μl; three times within 5 days) significantly caused delayed development and decreased intensity of clinical signs and pathological lesions, low viral load, significantly reduced Negri bodies (NBs) formation, and increased survival time in SRABV-infected mice[8].
References:
[1] Wang Y, Zhang S, Li H, et al. Small-molecule modulators of toll-like receptors[J]. Accounts of chemical research, 2020, 53(5): 1046-1055.
[2] Cheng K, Wang X, Yin H. Small-molecule inhibitors of the TLR3/dsRNA complex[J]. Journal of the American Chemical Society, 2011, 133(11): 3764-3767.
[3] Takemura N, Kawasaki T, Kunisawa J, et al. Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome[J]. Nature communications, 2014, 5(1): 3492.
[4] Lomphithak T, Choksi S, Mutirangura A, et al. Receptor-interacting protein kinase 1 is a key mediator in TLR3 ligand and Smac mimetic-induced cell death and suppresses TLR3 ligand-promoted invasion in cholangiocarcinoma[J]. Cell Communication and Signaling, 2020, 18(1): 161.
[5] Alcala A, Osborne B, Allen B, et al. Toll-like receptors in the mechanism of tributyltin-induced production of pro-inflammatory cytokines, IL-1β and IL-6[J]. Toxicology, 2022, 472: 153177.
[6] Mukherjee R, Bhattacharya A, Bojkova D, et al. Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection[J]. Journal of Biological Chemistry, 2021, 297(2).
[7] Neu C, Thiele Y, Horr F, et al. DAMPs released from proinflammatory macrophages induce inflammation in cardiomyocytes via activation of TLR4 and TNFR[J]. International journal of molecular sciences, 2022, 23(24): 15522.
[8] Sardana S, Singh K P, Saminathan M, et al. Effect of inhibition of Toll-like receptor 3 signaling on pathogenesis of rabies virus in mouse model[J]. Acta Tropica, 2022, 234: 106589.
CU CPT 4a 是一种有效的 Toll 样受体 3（TLR3）抑制剂，IC50值为3.44μM[1]。CU CPT 4a通过抑制TLR3/dsRNA复合物介导的下游信号通路，进而干扰素和促炎细胞因子（TNF-α、IL-1β和IL-6）的产生[2]。CU CPT 4a已广泛应用于动物模型中，以调节 TLR3 介导的炎症反应[3]。
在体外，用40μM的CU CPT 4a预处理KKU213细胞1小时，能显著抑制由2.5μg/ml Poly(I:C)（处理 12 小时）诱导的细胞侵袭[4]。用20µM的CU CPT 4a处理人外周血单核细胞1小时，可显著抑制Tributyltin (TBT)（25nM）诱导的IL-1β和IL-6 产生[5]。在SARS-CoV-2感染的Caco2细胞中，使用10µM的CU CPT 4a处理24小时，能够消除组胺对TBK1/IRF3信号通路的激活作用[6]。用40μM的CU CPT 4a处理小鼠心肌细胞24小时，降低了Caspase-3/7的活化水平，未减弱LPS刺激的细胞凋亡[7]。
在体内，通过腹腔注射CU CPT 4a（30μg/10μl；5天内注射3次）治疗Street rabies virus (SRABV) 感染的小鼠，能显著延缓疾病进展、减轻临床症状和病理损伤程度、降低病毒载量、显著减少内基氏体形成，并延长存活时间[8]。
| Cell experiment [1]: | |
Cell lines | Peripheral blood mononuclear cells (PBMCs) |
Preparation Method | PBMCs (at a concentration of 4×106 cells/0.67ml) were treated with CU CPT 4a (20μM) or the appropriate DMSO control for 1h and then exposed to TBT (25nM) for 24h. The cells were precipitated, the supernatant was collected, and the secretion of IL-1β or IL-6 in the supernatant was measured by enzyme-linked immunosorbent assay (ELISA). Cell precipitates were treated with lysis buffer and incubated on ice for 20min with vortexing every 5min. After a 20-min incubation period, lysates were centrifuged at 10,000rpm for 10min at 4°C in a microcentrifuge. The resulting lysates were collected to assess intracellular levels of IL-1β and IL-6 by Western blotting. |
Reaction Conditions | 20μM; 1h |
Applications | CU CPT 4a treatment reduced TBT-induced IL-1β and IL-6 production in PBMCs. |
| Animal experiment [2]: | |
Animal models | Young Swiss albino mice |
Preparation Method | Young Swiss albino mice, aged 2-3 weeks, were housed under controlled sterile environmental conditions. Mice were divided into three groups. Group I (SRABV + DMSO, n = 25) mice were intraperitoneally injected with 20μl of 100 LD50 SRABV with a 33-gauge needle on day 0 and simulated treatment with three intraperitoneal injections of 10μl DMSO within 5 days of infection. Group II (SRABV+CU CPT 4a, n = 25) mice were intraperitoneally injected with 20μl of 100 LD50 SRABV on day 0, and 10μl CU CPT 4a (30μg, dissolved in DMSO) was intraperitoneally injected three times within 5 days of infection. Group III (CU CPT 4a+DMSO, n = 21) mice received three injections of 30μl CU CPT 4a (30μg dissolved in DMSO) within 5 days of infection. Tissues were collected for analysis 15 days after infection. |
Dosage form | 30μg/10μl; three times within 5 days; i.p. |
Applications | CU CPT 4a treatment significantly inhibited TLR3 expression, resulting in delayed development and decreased intensity of clinical signs and pathological lesions, low viral load, significantly reduced NBs formation, and increased survival time in SRABV-infected mice. |
References: | |
| Cas No. | 1279713-77-7 | SDF | |
| 别名 | TLR3-IN-1 | ||
| 化学名 | (R,Z)-2-(((3-chloro-6-fluorobenzo[b]thiophen-2-yl)(hydroxy)methylene)amino)-3-phenylpropanoic acid | ||
| Canonical SMILES | ClC(C1=C(S2)C=C(F)C=C1)=C2/C(O)=N/[C@](C(O)=O)([H])CC3=CC=CC=C3 | ||
| 分子式 | C18H13ClFNO3S | 分子量 | 377.82 |
| 溶解度 | <37.78mg/ml in DMSO | 储存条件 | Store at 4°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 | 2.6468 mL | 13.2338 mL | 26.4676 mL |
| 5 mM | 529.4 μL | 2.6468 mL | 5.2935 mL |
| 10 mM | 264.7 μL | 1.3234 mL | 2.6468 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
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- Purity: >98.00%
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