Dusquetide
(Synonyms: SGX942) 目录号 : GC68403Dusquetide (SGX942) 是第一类天然防御调节因子 (IDR)。Dusquetide 通过与 p62 结合调节 PAMPs 和 DAMPs 的天然免疫应答。Dusquetide 在减轻炎症和增加细菌感染清除方面都显示出活性。
Cas No.:931395-42-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dusquetide (SGX942) is a first-in-class innate defense regulator (IDR). Dusquetide modulates the innate immune response to both PAMPs and DAMPs by binding to p62. Dusquetide shows activity in both reducing inflammation and increasing clearance of bacterial infection[1]. DAMPs: damage-associated molecular patterns; PAMPs: pathogen-associated molecular patterns
Dusquetide (SGX942) (25 mg/kg; i.v.; days 0, 4, 7, 10, and 14) shows no increase in tumor growth or worsening of survival and a trend towards decreased tumor growth and improvement in survival with radiation[1].
| Animal Model: | Female nude mice (MCF-7 tumor xenografts)[1] |
| Dosage: | 25 mg/kg |
| Administration: | I.v.; days 0, 4, 7, 10, and 14 |
| Result: | Showed no increase in tumor growth or worsening of survival and a trend towards decreased tumor growth and improvement in survival with radiation. |
[1]. Kudrimoti M, et al. Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study. J Biotechnol. 2016 De
| Cas No. | 931395-42-5 | SDF | Download SDF |
| 别名 | SGX942 | ||
| 分子式 | C25H47N9O5 | 分子量 | 553.7 |
| 溶解度 | H2O : 50 mg/mL (90.30 mM; Need ultrasonic) | 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 | 1.806 mL | 9.0302 mL | 18.0603 mL |
| 5 mM | 0.3612 mL | 1.806 mL | 3.6121 mL |
| 10 mM | 0.1806 mL | 0.903 mL | 1.806 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。
Dusquetide modulates innate immune response through binding to p62
Structure 2022 Aug 4;30(8):1055-1061.e7.PMID:PMC9357125DOI:10.1016/j.str.2022.05.003.
SQSTM1/p62 is an autophagic receptor that plays a major role in mediating stress and innate immune responses. Preclinical studies identified p62 as a target of the prototype innate defense regulator (IDR); however, the molecular mechanism of this process remains unclear. Here, we describe the structural basis and biological consequences of the interaction of p62 with the next generation of IDRs, Dusquetide. Both electrostatic and hydrophobic contacts drive the formation of the complex between Dusquetide and the ZZ domain of p62. We show that Dusquetide penetrates the cell membrane and associates with p62 in vivo. Dusquetide binding modulates the p62-RIP1 complex, increases p38 phosphorylation, and enhances CEBP/B expression without activating autophagy. Our findings provide molecular details underlying the IDR action that may help in the development of new strategies to pharmacologically target p62.
Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study
J Biotechnol 2016 Dec 10;239:115-125.PMID:27746305DOI:10.1016/j.jbiotec.2016.10.010.
Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that Dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of Dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of Dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.
Dusquetide: Reduction in oral mucositis associated with enduring ancillary benefits in tumor resolution and decreased mortality in head and neck cancer patients
Biotechnol Rep (Amst) 2017 May 17;15:24-26.PMID:28649557DOI:10.1016/j.btre.2017.05.002.
Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating Dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that Dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified.
Protocol to identify drug-binding sites in proteins using solution NMR spectroscopy
STAR Protoc 2022 Dec 16;3(4):101842.PMID:36595882DOI:10.1016/j.xpro.2022.101842.
Dusquetide is a next-generation IDR (innate defense regulator) targeting the major autophagy receptor protein SQSTM1/p62 and modulating the innate immune response. Here, we describe a protocol for determining dusquetide-binding sites of p62 by solution NMR spectroscopy. Step-by-step technique details were provided, including sample preparation, NMR experiment setup, data processing, and binding site analysis. This protocol could be applied to characterize other small molecules targeting the ZZ domain of p62 (9 kDa) or other proteins containing ZZ domains. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).