WKYMVm
目录号 : GC16498
A synthetic peptide agonist of FPR1 and FPR2
Cas No.:187986-17-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
human pulmonary microvascular endothelial cells |
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Preparation Method |
In the hydrogen peroxide (H2O2)-induced oxidative stress in lung cell assay, cells were exposed to 100 µM H2O2 with WKYMVm treatment. After incubation with WKYMVm for 24 hours in 96-well plates, the cell counting kit (CCK)-8 assay was carried out to determine the relative cell proliferation rate (%), according to the manufacturer’s instructions. |
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Reaction Conditions |
100 µM, 24 h |
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Applications |
In human pulmonary microvascular endothelial cells (HULEC-5a) and primary murine pulmonary endothelial and epithelial cells, 1 and 100 µM WKYMVm treatments significantly increased proliferation in both the control and H2O2-exposed groups. |
| Animal experiment [2]: | |
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Animal models |
male C57/BL6J mice |
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Preparation Method |
A total of 20 male C57/BL6 mice, eight‐week‐old, were split randomly into four equal groups: sham, LPS, low‐dose WKYMVm (4 mg/kg bodyweight) and high‐dose WKYMVm (8 mg/kg bodyweight). The sham and LPS group were injected with PBS and LPS (5 mg/kg bodyweight), respectively. Predetermined WKYMVm doses were mixed with LPS and injected into the mice in combination. Injections were performed subcutaneously against the skull altogether 7 times with 48 hours intervals between applications. |
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Dosage form |
4 mg/kg and 8 mg/kg;s.c. |
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Applications |
WKYMVm protected against LPS‐induced bone loss in vivo. |
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References: [1]. Kim YE, et al. WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice. Sci Rep. 2019 May 2;9(1):6815. [2]. Hu J, et al. The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway. J Cell Mol Med. 2020 Jan;24(2):1893-1905. |
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WKYMVm is a potent N-formyl peptide receptor (FPR1) and FPRL1/2 agonist, and also activate phosphoinositide hydrolysis in undifferentiated HL-60 cells.[1]
In vitro efficacy test indicated that treatment with 0.01, 0.1, 1 and 10 μmol/L WKYMVm for 24 hours or 48 hours obviouly suppressed RANKL‐induced mature osteoclasts.[3] In vitro, treatment with 10 μM WKYMVm to stimulate FPR2 can induce p47phox phosphorylation in IMR90 fibroblasts and in human lung cancer cells, which is considered the key event for NADPH oxidase-dependent superoxide generation. Moreover, 10 μM WKYMVm to stimulate also induced NADPH oxidase-dependent superoxide generation with maximal production occurring at 2 min.[6]
In vivo experiment it shown that treatment with 2.5- and 5 mg/kg/d daily over four days intraperitoneally in ALI mice decreased the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β, while it increased the MPO and NO release by differentiated HL-60 neutrophil-like cells.[2].
Intramuscular injection of 10?5 mol/l WKYMVm improves blood perfusion and provides protection from tissue damage in the ischemic hind limb.[4] In vivo, treatment with 8 mg/kg WKYMVm subcutaneously (at 0, 12, 24, 36, 48 and 60h) effectively attenuated the DSS-induced increase in the bleeding score and the stool score and protects dextran sodium sulfate (DSS)-induced experimental ulcerative colitis.[5] In addition, administration of 4 mg/kg WKYMVm, to septic mice strongly increased neutrophil number through augmented emergency granulopoiesis[7].
References:
[1]. Christophe T, et al. The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem. 2001 Jun 15;276(24):21585-93.
[2]. Lee H, et al. WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway. Biochem Biophys Res Commun. 2020 Dec 10;533(3):313-318.
[3]. Hu J, et al. The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway. J Cell Mol Med. 2020 Jan;24(2):1893-1905.
[4]. Heo SC, et al. WKYMVm-induced activation of formyl peptide receptor 2 stimulates ischemic neovasculogenesis by promoting homing of endothelial colony-forming cells. Stem Cells. 2014 Mar;32(3):779-90.
[5]. Kim SD, et al. The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative colitis. Exp Mol Med. 2013 Sep 13;45(9):e40.
[6]. Cattaneo F, et al. WKYMVm-induced cross-talk between FPR2 and HGF receptor in human prostate epithelial cell line PNT1A. FEBS Lett. 2013 May 21;587(10):1536-42.
[7]. Kim HS, et al. Activation of formyl peptide receptor 2 by WKYMVm enhances emergency granulopoiesis through phospholipase C activity. BMB Rep. 2018 Aug;51(8):418-423.
WKYMVm 是一种有效的 N-甲酰肽受体 (FPR1) 和 FPRL1/2 激动剂，还可以激活未分化 HL-60 细胞中的磷酸肌醇水解。[1]
体外药效试验表明，0.01、0.1、1和10μmol/L WKYMVm处理24小时或48小时明显抑制RANKL诱导的成熟破骨细胞。[3]用 10 μM WKYMVm 刺激 FPR2 可诱导 IMR90 成纤维细胞和人肺癌细胞中的 p47phox 磷酸化，这被认为是 NADPH 氧化酶依赖性超氧化物生成的关键事件。此外，10 μM WKYMVm 刺激还诱导 NADPH 氧化酶依赖性超氧化物的产生，最大产生发生在 2 分钟。[6]
体内实验表明，每天 2.5 和 5 mg/kg/d 腹膜内注射 ALI 小鼠 4 天可降低促炎细胞因子 TNF-α、IL-6 和 IL-1β 的水平，同时增加分化的 HL-60 中性粒细胞样细胞释放 MPO 和 NO。[2].
肌内注射 10-5 mol/l WKYMVm 可改善血液灌注并保护缺血后肢免受组织损伤。[4] 在体内，皮下注射 8 mg/kg WKYMVm (在 0、12、24、36、48 和 60h 时）有效减弱了 DSS 引起的出血评分和粪便评分的增加，并保护了葡聚糖硫酸钠 (DSS) 引起的实验性溃疡性结肠炎。[5]< /sup> 此外，对败血症小鼠施用 4 mg/kg WKYMVm 通过增强紧急粒细胞生成显着增加中性粒细胞数量[7]。
| Cas No. | 187986-17-0 | SDF | |
| 化学名 | (S)-6-amino-2-((S)-2-amino-3-(1H-indol-3-yl)propanamido)-N-((5R,8S,11S,14S)-5-carbamoyl-15-(4-hydroxyphenyl)-8-isopropyl-11-(2-(methylthio)ethyl)-7,10,13-trioxo-2-thia-6,9,12-triazapentadecan-14-yl)hexanamide | ||
| Canonical SMILES | O=C([C@H](CCCCN)NC([C@H](CC1=CNC2=CC=CC=C12)N)=O)N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](C(N)=O)CCSC)=O)C(C)C)=O)CCSC)=O)CC(C=C3)=CC=C3O | ||
| 分子式 | C41H61N9O7S2 | 分子量 | 856.11 |
| 溶解度 | Soluble to 2 mg/ml in Water | 储存条件 | -20°C, protect from light |
| 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 | 1.1681 mL | 5.8404 mL | 11.6807 mL |
| 5 mM | 0.2336 mL | 1.1681 mL | 2.3361 mL |
| 10 mM | 0.1168 mL | 0.584 mL | 1.1681 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。
Therapeutic potential of WKYMVm in diseases
The synthetic hexapeptide WKYMVm, screened from a synthetic peptide library, has been identified as an agonist of FPRs with the strongest activating effect on FPR2. WKYMVm plays an anti-inflammatory role in most inflammatory diseases by increasing the chemotaxis of phagocytes and regulating the secretion of inflammatory factors. WKYMVm can inhibit or promote the progression of different types of tumors, which depends on the regulation of WKYMVm on various components such as immune cells, inflammatory factors, chemokines, and tumor epithelial cells. Another major function of WKYMVm is to promote angiogenesis, which is reflected in its therapeutic value in ischemic diseases, wound healing and bone repair. In addition to the above functions, this paper also reviews the effects of WKYMVm on fibrosis, insulin resistance, osteolytic diseases and neurodegenerative diseases. By summarizing related studies, this review can increase people's comprehensive understanding of WKYMVm, promote its broad and in-depth research, and help to exert its therapeutic value as soon as possible.
WKYMVm Works by Targeting Immune Cells
WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met) is a synthetic hexapeptide identified as a potent agonist of FPRs. FPRs are widely expressed on the cell membrane of immune cells. Therefore, WKYMVm participates in the regulation of immune cells by activating FPRs, and plays a therapeutic role in infections, tumors, autoimmune diseases and so on. WKYMVm can promote the chemotactic migration, increase the bactericidal activity of neutrophils and monocytes. WKYMVm also regulates the number and polarization of macrophages, affects the maturation of DCs and the differentiation of T cells, and promotes the activation and chemotaxis of NK cells. These functions make WKYMVm a candidate drug for immunotherapy. In this paper, we summarize the regulatory effects and underlying mechanisms of WKYMVm on six immune cells (neutrophils, monocytes, macrophages, DCs, T cells and NK cells) to increase comprehensive understanding and promote further research on WKYMVm.
WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway
Formyl peptide receptors (FPRs) are mainly expressed on leucocytes and sense microbe-associated molecular pattern (MAMP) molecules, thereby regulating leukocyte chemotaxis and activation. The formyl peptide receptor 2 (FPR2) selective agonist WKYMVm (Trp-Lys-Met-Val-D-Met) has shown potent pro-angiogenic, anti-inflammatory, and anti-apoptotic properties. In this study, we investigated whether WKYMVm exhibits bactericidal activity during neutrophil accumulation in acute lung injury (ALI) in mice and determined its cellular signaling pathways in HL-60 neutrophil-like cells. A daily intraperitoneal treatment of ALI mice with WKYMVm (2.5- and 5 mg/kg/d) daily over four days decreased the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β, while it increased the MPO and NO release by differentiated HL-60 neutrophil-like cells. The IRF1 level and STAT1 phosphorylation at S727 were increased in the lungs of mice with ALI treated with WKYMVm. Lung histology induced by ALI was unaffected by treatment with WKYMVm. In vitro, WKYMVm increased MPO, NO, and SOD activity, as well as IRF1 and STAT1 phosphorylation at Ser727. Taken together, our data suggest therapeutic potential of WKYMVm, via FPR2-dependent regulation of STAT1/IRF1, in ALI.
WKYMVm/FPR2 Alleviates Spinal Cord Injury by Attenuating the Inflammatory Response of Microglia
Spinal cord injury (SCI) is a common traumatic disease of the nervous system. The pathophysiological process of SCI includes primary injury and secondary injuries. An excessive inflammatory response leads to secondary tissue damage, which in turn exacerbates cellular and organ dysfunction. Due to the irreversibility of primary injury, current research on SCI mainly focuses on secondary injury, and the inflammatory response is considered the primary target. Thus, modulating the inflammatory response has been suggested as a new strategy for the treatment of SCI. In this study, microglial cell lines, primary microglia, and a rat SCI model were used, and we found that WKYMVm/FPR2 plays an anti-inflammatory role and reduces tissue damage after SCI by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways. FPR2 was activated by WKYMVm, suppressing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by inhibiting M1 microglial polarization. Moreover, FPR2 activation by WKYMVm could reduce structural disorders and neuronal loss in SCI rats. Overall, this study illustrated that the activation of FPR2 by WKYMVm repressed M1 microglial polarization by suppressing the ERK1/2 and NF-κB signaling pathways to alleviate tissue damage and locomotor decline after SCI. These findings provide further insight into SCI and help identify novel treatment strategies.
Bam32/DAPP1-Dependent Neutrophil Reactive Oxygen Species in WKYMVm-Induced Microvascular Hyperpermeability
B cell adaptor molecule of 32 kDa (Bam32), known as dual adapter for phosphotyrosine and 3-phosphoinositides 1 (DAPP1), has been implicated in regulating lymphocyte proliferation and recruitment during inflammation. However, its role in neutrophils during inflammation remains unknown. Using intravital microscopy, we examined the role of Bam32 in formyl peptide receptor agonist WKYMVm-induced permeability changes in post-capillary venules and assessed simultaneously neutrophil adhesion and emigration in cremaster muscles of Bam32-deficient (Bam32-/-) and wild-type (WT) control mice. We observed significantly reduced WKYMVm-induced microvascular hyperpermeability accompanied by markedly decreased neutrophil emigration in Bam32-/- mice. The Bam32-specific decrease in WKYMVm-induced hyperpermeability was neutrophil-dependent as this was verified in bone marrow transplanted chimeric mice. We discovered that Bam32 was critically required for WKYMVm-induced intracellular and extracellular production of reactive oxygen species (ROS) in neutrophils. Pharmacological scavenging of ROS eliminated the differences in WKYMVm-induced hyperpermeability between Bam32-/- and WT mice. Deficiency of Bam32 decreased WKYMVm-induced ERK1/2 but not p38 or JNK phosphorylation in neutrophils. Inhibition of ERK1/2 signaling cascade suppressed WKYMVm-induced ROS generation in WT neutrophils and microvascular hyperpermeability in WT mice. In conclusion, our study reveals that Bam32-dependent, ERK1/2-involving ROS generation in neutrophils is critical in WKYMVm-induced microvascular hyperpermeability during neutrophil recruitment.