P4pal10

PAR4[1]

P4pal10是一种pepducin，其肽序列与蛋白酶激活受体4（PAR4）的第三细胞内环的一部分相同，PAR4作为PAR4拮抗剂。通过血小板聚集、细胞内Ca2+释放或InsP产生测量，P4pal10没有激动剂活性，但人血小板与P4pal10的预孵育完全阻断了对PAR4激活剂的聚集。将P4Pal10输注到小鼠中延长了出血时间并保护其免受全身血小板活化，并且在心肌损伤的大鼠模型中，当在缺血之前、期间和之后给予P4Pal10治疗时，缺血之前的P4Pal10处理显著减小了梗死面积。P4Pal10还抑制Galphai偶联的FPR2下游的信号传导。

我们评估了蛋白酶激活受体4（标准杆数（4））在啮齿类动物爪炎症模型中的潜在作用，重点关注炎症的两个主要特征：（1）水肿和（2）粒细胞募集。2标准杆数（4）拮抗剂（Pepducin P4pal-10；棕榈酰-SGRRYGHALR-NH（2））减少了大鼠后爪局部施用卡拉胶诱导的水肿和粒细胞募集，表明标准杆数（4）在该炎症模型中的关键作用。3此外，在小鼠后爪内注射标准杆数（4）激动剂（AYPGKF-NH（2）），但不是其标准的标准杆数（4）-无活性肽对照（YAPGKF-NH（2），引起了以水肿（爪厚度增加）和粒细胞募集（爪髓过氧化物酶活性增加）为特征的炎症反应。在用pepducin P4pal10预处理的小鼠中抑制了标准杆数（4）激动剂诱导的效应。4这些标准杆数（4）激动剂介导的作用不受NO产生或前列腺素释放抑制剂（分别为L-NAME和消炎痛）预处理的影响。5然而，中性粒细胞的选择性免疫耗竭显著减少了标准杆数（4）激动剂诱导的水肿形成。6此外，AYPGKF-NH（2）诱导的水肿也通过用激肽B（2）受体拮抗剂（艾蒂班特）或组织或血浆激肽释放酶抑制剂（分别为FE999024和FE999026）预处理而减少，但不用激素B（1）受体拮抗物（SSR240612）预处理。7我们得出结论：（1）标准杆数（4）在炎症反应中起着重要作用，因为它介导了炎症的一些特征；（2）标准杆数（4）介导的水肿依赖于中性粒细胞和激肽释放肽-激肽系统成分的募集。[1]

[1]. Houle S, et al. Neutrophils and the kallikrein-kinin system in proteinase-activated receptor 4-mediated inflammation in rodents. Br J Pharmacol. 2005 Nov;146(5):670-8.

C65H112N22O13

1409.72

1021346-05-3

{Pal}-Ser-Gly-Arg-Arg-Tyr-Gly-His-Ala-Leu-Arg-NH2

{Pal}-SGRRYGHALR-NH2

C(N)(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC1N=CNC=1)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H](CO)NC(=O)CCCCCCCCCCCCCCC

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。