LXW7
目录号 : GC36500
LXW7 是一种八聚二硫环肽，为整合素 αvβ3 的配体，能够有效、特异性地靶作用于内皮祖细胞 (EPCs) 和内皮细胞 (ECs)。在 ECs 细胞中，LXW7 可增强 VEGFR-2 的磷酸化和 ERK1/2 的活化。
Cas No.:1313004-77-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LXW7 is an octamer disulfide cyclic peptide, also a αvβ3 integrin ligand, acts as a potent and specific endothelial progenitor cells (EPCs) and endothelial cells (ECs) targeting ligand. LXW7 increases phosphorylation of VEGFR-2 and activation of ERK1/2[1]. αvβ3[1]
[1]. Hao D, et al. Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration. ACS Chem Biol. 2017 Apr 21;12(4):1075-1086.
| Cas No. | 1313004-77-1 | SDF | |
| 分子式 | C29H48N12O12S2 | 分子量 | 820.89 |
| 溶解度 | Soluble in DMSO | 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 | 1.2182 mL | 6.091 mL | 12.1819 mL |
| 5 mM | 0.2436 mL | 1.2182 mL | 2.4364 mL |
| 10 mM | 0.1218 mL | 0.6091 mL | 1.2182 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。
CeO2@PAA-LXW7 Attenuates LPS-Induced Inflammation in BV2 Microglia
Cell Mol Neurobiol 2019 Nov;39(8):1125-1137.PMID:31256326DOI:10.1007/s10571-019-00707-2.
Microglia are the inherent immune effector cells in the central nervous system (CNS), are activated rapidly when the CNS is stimulated by ischaemia, infection, injury, etc. and participate in and aggravate the development of inflammatory reactions in the CNS. During the process of microglial activation, inflammatory factors such as TNF-α and IL-1β and an abundance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), are released by damaged nerve cells. LXW7 is a small molecule peptide and specifically binds with integrin αvβ3. Cerium oxide nanoparticles (nanoceria) are strong free radical scavengers and are widely used in many studies. In this research, a model of inflammation was established using lipopolysaccharide (LPS) to induce BV2 microglia activation, and the effects of CeO2@PAA (synthetic nanoscale cerium oxide particles), LXW7 and CeO2@PAA-LXW7 were evaluated. We detected the expression level of inflammatory factors, the release of NO in BV2 cells and the generation of intracellular ROS. The expression levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) and their phosphorylated proteins were detected in BV2 microglia. We found that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 all effectively inhibited the activation of BV2 microglia, reduced the production of cytokines and the release of NO and reduced the production of intracellular ROS. The three treatments all inhibited the phosphorylation of FAK and STAT3 in BV2 microglia. Regarding these effects, CeO2@PAA-LXW7 was more effective than the other two monotherapies. Our data indicate that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 can exert a neuroprotective function by inhibiting the inflammatory response of LPS-induced BV2 microglia. LXW7 may inhibit the activation of FAK and STAT3 signals in combination with integrin αvβ3 to restrain neuroinflammation and the antioxidative stress effect of cerium oxide; hence, CeO2@PAA-LXW7 can exert a more robust anti-inflammatory and neuroprotective effect via synergistically suppressing the ability of LXW7 to influence the integrin pathway and the free radical-scavenging ability of CeO2@PAA.
LXW7 attenuates inflammation via suppressing Akt/nuclear factor kappa B and mitogen-activated protein kinases signaling pathways in lipopolysaccharide-stimulated BV2 microglial cells
Int Immunopharmacol 2019 Dec;77:105963.PMID:31732449DOI:10.1016/j.intimp.2019.105963.
Microglia activation is closely linked to ischemia, various chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis), and many other central nervous system diseases. Accumulating evidence suggests that depressing the microglial inflammatory response could be an effective treatment for inflammatory disorders. The integrin αvβ3 inhibitor LXW7 has a neuroprotective effect; however, its anti-inflammatory effects and underlying mechanism remain unclear. Thus, we examined whether LXW7 would inhibit inflammatory cytokines and mediators, and we evaluated the potential mechanisms of its neuroprotective effects. Nitrite analysis revealed LXW7 reduced the nitric oxide (NO) level. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) suggested that LXW7 suppressed the expression of proinflammatory genes for tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and anti-inflammatory gene interleukin 10 (IL-10) at the messenger ribonucleic acid level. Enzyme-linked immunosorbent assay results demonstrated that LXW7 treatment reduced the expression of prostaglandin E2 (PGE2), TNF-α, IL-1β and IL-10 at the protein level. Western blotting was conducted to confirm the upregulation of inflammatory factors, including iNOS and COX-2 at the protein level. LXW7 inhibited major genes in the Akt/NF-κB and c-Jun NH2-terminal kinase/ mitogen-activated protein kinases (JNK/MAPK) signaling pathways. Immunofluorescence revealed that LXW7 inhibited the nuclear translocation of nuclear factor kappa B (NF-κB). Thus, LXW7 effectively alleviated LPS-induced inflammatory damage and had neuroprotective effects. The anti-inflammatory effects of LXW7 may be associated with the inhibition of microglial activation via Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor. The present study's findings suggest that LXW7 has a substantial therapeutic potential for treating inflammatory and neurodegenerative diseases.
LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats
Braz J Med Biol Res 2016 Aug 1;49(9):e5287.PMID:27533766DOI:10.1590/1414-431X20165287.
Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250-280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.
Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells
Neurochem Res 2018 Jul;43(7):1439-1453.PMID:29882125DOI:10.1007/s11064-018-2559-y.
CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2@PAA-LXW7, a new compound that couples CeO2@PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2O2-induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO2@PAA, and CeO2@PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H2O2-induced injury. We used H2O2-induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO2@PAA-LXW7. In this study, LXW7, CeO2@PAA, and CeO2@PAA-LXW7 inhibit H2O2-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H2O2-induced NGF-differentiated PC12 cells, whereas LXW7, CeO2@PAA, and CeO2@PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO2@PAA-LXW7 on H2O2-induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO2@PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H2O2-induced NGF-differentiated PC12 cells. LXW7, CeO2@PAA, and CeO2@PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H2O2 in NGF-differentiated PC12 cells. CeO2@PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO2@PAA.
Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats
Curr Med Sci 2018 Feb;38(1):144-152.PMID:30074164DOI:10.1007/s11596-018-1858-5.
Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively. Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion. Drug treatment was intravenously administered via the caudal vein 1 h after occlusion. Rats were randomly divided into the following 4 groups: bLXW7-CeNP treatment group (0.5 mg/kg); CeNP treatment group (0.5 mg/kg); control saline group; and sham group. Brains were harvested 24 h after reperfusion, and the neurologic deficit scores, infarction volume, blood-brain barrier (BBB) disruption, and the level of oxidative stress and apoptosis were determined. Results showed that the bLXW7-CeNP and CeNP treatments could improve neurologic deficit scores, infarction volume, BBB disruption, and the level of oxidative stress and apoptosis. Compound bLXW7-CeNP treatment exhibited better effects than CeNp treatment and showed remarkable statistical differences in the infarction volume, the degree of BBB breakdown, the apoptosis and oxidative stress, apart from neurologic deficit scores. Thus, we concluded that bLXW7-CeNP protects against acute cerebral ischemia/reperfusion injury. BLXW7, as a ligand of integrin αvβ3, may be able to effectively localize the anti-oxidant CeNPs to the ischemic penumbra region, which may provide more adequate opportunities for CeNPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.