Home>>Signaling Pathways>> Angiogenesis>> Integrin>>ATN-161

ATN-161 Sale

目录号 : GC34133

An integrin receptor antagonist

ATN-161 Chemical Structure

Cas No.:262438-43-7

规格 价格 库存 购买数量
10mg
¥3,353.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment:

Ninety-six well microtiter plates are coated with fibronectin(20 μg/mL) overnight at 4°C. HUVECs are then trypsinized as described above and resuspended in 1% FBS-MEM for cell counting. Cell suspensions with 10,000 cells/mL are prepared in serum-reduced conditions by using 1% FBS-MEM, or 1% FBS-MEM containing either ATN-161 (1 μM) or ATN-163 (scrambled peptide as control; 1μM) to allow interference by the peptide during the ligand binding process (i.e., binding of α5β1 to fibronectin). Cells are thereafter plated into each well (2,000 cells/well in 200 μL) of the fibronectin-coated 96-well plates. Cells are incubated at 37°C for 48 hr under these serum-reduced conditions in order to evaluate effects of ATN-161 on EC survival and proliferation. Estimation of cell number is performed by adding 40 μL MTT to each well and incubating for 2 hr at 37°C. Media is then removed, cells are solubilized in 100 μL DMSO and optical density is measured at 560 nm. Experiments are performed in triplicate[1].

Animal experiment:

Mice[1] Eight-week-old male BALB/c mice are acclimated for 1 week while caged in groups of 5. Mice are fed a diet of animal chow and water ad libitum throughout the experiment. CT-26 cells (10,000 cells in 50 μL HBSS) are injected into the spleens of 40 BALB/c mice to produce liver metastases. Mice are randomly assigned to 1 of 4 treatment groups (10 mice per group): (A) control (saline/saline), (B) 5-FU alone, (C) ATN-161 alone and (D) ATN-161 plus 5-FU. Body weight at randomization is similar among groups. Treatment with ATN-161 (100 mg/kg) or saline is started on day 4 after CT-26-cell injection and is administered every third day thereafter by intraperitoneal injection. In previous studies, administration of the peptide every third day has been shown to be adequate for sustained inhibition of integrin α5β1 activity. Mice are allowed to recover for 1 week from the surgical procedure and effects of anesthesia with pentobarbital (Nembutal, 50 mg/kg). On day 7, mice are anaesthetized again and osmotic pumps.

References:

[1]. Stoeltzing O, et al. Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer. 2003 Apr 20;104(4):496-503.
[2]. Wang W, et al. The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo. Invest Ophthalmol Vis Sci. 2011 Sep 14;52(10):7213-20.

产品描述

ATN-161 is a peptide derived from fibronectin and an integrin αVβ3 and αVβ5 antagonist.1 It binds to αVβ3 and αVβ5 receptors (Kds = 0.69 and 1 ?M, respectively) in MDA-MB-231 breast cancer cells, as well as inhibits the interaction between αVβ5 and human angiotensin-converting enzyme 2 (ACE2) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a concentration-dependent manner in cell-free assays.1,2 ATN-161 reduces viral titers in Vero E6 cells infected with SARS-CoV-2 (EC50 = 3.16 ?M).2 It inhibits VEGF-induced migration and capillary tube formation of primary human choroidal endothelial cells when used at a concentration of 0.1 ?M.3 ATN-161 (1 mg/kg) reduces tumor growth and metastasis in an MDA-MB-231 mouse xenograft model and infarct volume and edema in a mouse model of ischemic stroke induced by middle cerebral artery occlusion (MCAO).1,4

1.Khalili, P., Arakelian, A., Chen, G., et al.A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivoMol. Cancer Ther.5(9)2271-2280(2006) 2.Beddingfield, B.J., Iwanaga, N., Chapagain, P.P., et al.The integrin binding peptide, ATN-161, as a novel therapy for SARS-CoV-2 infectionJACC Basic Transl. Sci.6(1)1-8(2021) 3.Wang, W., Wang, F., Lu, F., et al.The antiangiogenic effects of integrin α5β1 inhibitor (ATN-161) in vitro and in vivoInvest. Ophthalmol. Vis. Sci.52(10)7213-7220(2011) 4.Edwards, D.N., Salmeron, K., Lukins, D.E., et al.Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic strokeJ. Cereb. Blood Flow Metab.40(8)1695-1708(2020)

Chemical Properties

Cas No. 262438-43-7 SDF
Canonical SMILES O=C(N)C[C@@H](C(N)=O)NC([C@H](CS)NC([C@H](CO)NC([C@H](CC1=CNC=N1)NC([C@H]2N(C(C)=O)CCC2)=O)=O)=O)=O
分子式 C23H35N9O8S 分子量 597.64
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。
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。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 1.6732 mL 8.3662 mL 16.7325 mL
5 mM 0.3346 mL 1.6732 mL 3.3465 mL
10 mM 0.1673 mL 0.8366 mL 1.6732 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

ATN-161 Ameliorates Ischemia/Reperfusion-induced Oxidative Stress, Fibro-inflammation, Mitochondrial damage, and Apoptosis-mediated Tight Junction Disruption in bEnd.3 Cells

Inflammation 2021 Dec;44(6):2377-2394.PMID:34420157DOI:10.1007/s10753-021-01509-9.

We have previously demonstrated the significance of endothelial cell-expressed α5β1 integrin in ischemic stroke, having shown that α5β1 integrin endothelial cell-selective knockout mice are significantly resistance to ischemic stroke injury via preservation of the tight junction protein claudin-5 and subsequent stabilization of the blood-brain barrier (BBB). In addition, inhibition of α5β1 by the small peptide noncompetitive integrin α5 inhibitor, ATN-161, is beneficial in a mouse model of ischemic stroke through reduction of infarct volume, edema, stabilization of the BBB, and reduced inflammation and immune cell infiltration into the brain. In continuation with our previous findings, we have further evaluated the mechanistic role of ATN-161 in vitro and found that oxygen and glucose deprivation and reperfusion (OGD/R)-induced inflammation, oxidative stress, apoptosis, mitochondrial depolarization, and fibrosis attenuate tight junction integrity via induction of α5, NLRP3, p-FAK, and p-AKT signaling in mouse brain endothelial cells. ATN-161 treatment (10 µM) effectively inhibited OGD/R-induced extracellular matrix (ECM) deposition by reducing integrin α5, MMP-9, and fibronectin expression, as well as reducing oxidative stress by reducing mitochondrial superoxide radicals, intracellular ROS, inflammation by reducing NLRP3 inflammasome, tight junction loss by reducing claudin-5 and ZO-1 expression levels, mitochondrial damage by inhibiting mitochondrial depolarization, and apoptosis via regulation of p-FAK and p-AKT levels. Taken together, our results further support therapeutically targeting α5 integrin with ATN-161, a safe, well-tolerated, and clinically validated peptide, in ischemic stroke.

Penta-peptide ATN-161 based neutralization mechanism of SARS-CoV-2 spike protein

Biochem Biophys Rep 2021 Dec;28:101170.PMID:34778573DOI:10.1016/j.bbrep.2021.101170.

SARS-CoV-2 has become a big challenge for the scientific community worldwide. SARS-CoV-2 enters into the host cell by the spike protein binding with an ACE2 receptor present on the host cell. Developing safe and effective inhibitor appears an urgent need to interrupt the binding of SARS-CoV-2 spike protein with ACE2 receptor in order to reduce the SARS-CoV-2 infection. We have examined the penta-peptide ATN-161 as potential inhibitor of ACE2 and SARS-CoV-2 spike protein binding, where ATN-161 has been commercially approved for the safety and possess high affinity and specificity towards the receptor binding domain (RBD) of S1 subunit in SARS-CoV-2 spike protein. We carried out experiments and confirmed these phenomena that the virus bindings were indeed minimized. ATN-161 peptide can be used as an inhibitor of protein-protein interaction (PPI) stands as a crucial interaction in biological systems. The molecular docking finding suggests that the binding energy of the ACE2-spike protein complex is reduced in the presence of ATN-161. Protein-protein docking binding energy (-40.50 kcal/mol) of the spike glycoprotein toward the human ACE2 and binding of ATN-161 at their binding interface reduced the biding energy (-26.25 kcal/mol). The finding of this study suggests that ATN-161 peptide can mask the RBD of the spike protein and be considered as a neutralizing candidate by binding with the ACE2 receptor. Peptide-based masking of spike S1 protein (RBD) and its neutralization is a highly promising strategy to prevent virus penetration into the host cell. Thus masking of the RBD leads to the loss of receptor recognition property which can reduce the chance of infection host cells.

SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders

Cytokine Growth Factor Rev 2021 Apr;58:1-15.PMID:33674185DOI:10.1016/j.cytogfr.2021.02.002.

SARS-CoV-2 is a novel coronavirus that severely affects the respiratory system, is the cause of the COVID-19 pandemic, and is projected to result in the deaths of 2 million people worldwide. Recent reports suggest that SARS-CoV-2 also affects the central nervous system along with other organs. COVID-19-associated complications are observed in older people with underlying neurological conditions like stroke, Alzheimer's disease, and Parkinson's disease. Hence, we discuss SARS-CoV-2 viral replication and its inflammation-mediated infection. This review also focuses on COVID-19 associated neurological complications in individuals with those complications as well as other groups of people. Finally, we also briefly discuss the current therapies available to treat patients, as well as ongoing available treatments and vaccines for effective cures with a special focus on the therapeutic potential of a small 5 amino acid peptide (PHSCN), ATN-161, that inhibits SARS-CoV-2 spike protein binding to both integrin α5β1 and α5β1/hACE2.

ATN-161 Peptide Functionalized Reversibly Cross-Linked Polymersomes Mediate Targeted Doxorubicin Delivery into Melanoma-Bearing C57BL/6 Mice

Mol Pharm 2017 Aug 7;14(8):2538-2547.PMID:28005375DOI:10.1021/acs.molpharmaceut.6b00800.

PHSCN peptide (licensed as ATN-161) is an effective α5β1 integrin inhibitor that has advanced to phase II clinical trials to treat solid tumors. Here we developed ATN-161 functionalized self-cross-linkable and intracellularly de-cross-linkable polymersomes (ATN/SCID-Ps) for highly efficient and targeted delivery of doxorubicin hydrochloride (DOX·HCl) into B16F10 melanoma-bearing C57BL/6 mice. ATN/SCID-Ps exhibited a high loading capacity of DOX·HCl. The size of DOX-loaded ATN/SCID-Ps (DOX-ATN/SCID-Ps) decreased from 150 to 88 nm with increasing ATN surface densities from 0 to 100% (mol/mol). DOX-ATN/SCID-Ps were robust with low drug leakage under physiological conditions while quickly releasing DOX with the addition of 10 mM glutathione. MTT assay results displayed that DOX-ATN/SCID-Ps induced ATN density-dependent antitumor activity to α5β1 integrin overexpressing B16F10 melanoma cells, in which 56% ATN-161 was optimal. Flow cytometry and CLSM studies revealed significantly more efficient internalization and cytoplasmic DOX release in B16F10 cells for DOX-ATN/SCID-Ps than for DOX-SCID-Ps (nontargeting control) as well as clinically used pegylated liposomal doxorubicin (DOX-LPs). DOX-ATN/SCID-Ps displayed a long blood circulation time (elimination half-life = 4.13 h) and 4 times higher DOX accumulation in B16F10 bearing C57BL/6 mice than DOX-LPs. Interestingly, DOX-ATN/SCID-Ps exhibited a superior maximum-tolerated dose of over 100 mg DOX·HCl/kg, 10 times higher than DOX-LPs. Remarkably, DOX-ATN/SCID-Ps could significantly inhibit the growth of aggressive B16F10 melanoma with little adverse effects via either multiple or single injection of total dosage of 100 mg DOX·HCl/kg, resulting in greatly improved survival rates as compared to DOX-LPs. ATN/SCID-Ps are appealing nanovehicles for targeted chemotherapy of α5β1 integrin positive solid tumors.

ATN-161 as an Integrin α5β1 Antagonist Depresses Ocular Neovascularization by Promoting New Vascular Endothelial Cell Apoptosis

Med Sci Monit 2018 Aug 22;24:5860-5873.PMID:30133427DOI:10.12659/MSM.907446.

BACKGROUND ATN-161 (Ac-PHSCN-NH2), an antagonist of integrin α5β1, has shown an important influence in inhibiting tumor angiogenesis and metastasis of other tumor types. However, the mechanism of action of ATN-161 and whether it can inhibit ocular neovascularization (NV) are unclear. This study investigated the role of ATN-161 in regulating ocular angiogenesis in mouse models and explored the underlying signaling pathway. MATERIAL AND METHODS An oxygen-induced retinopathy (OIR) mouse model and a laser-induced choroidal neovascularization (CNV) mouse model were used to test integrin a5b1 expression and the effect of ATN-161 on ocular NV by immunofluorescence staining, Western blot analysis, and flat-mount analysis. The activation of nuclear factor-κB (NF-κB), matrix metalloproteinase-2/9 (MMP-2/9), and cell apoptosis were detected by immunofluorescence staining, Western blot, real-time RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). The cell proliferation was detected by BrdU labeling. RESULTS In OIR and CNV mice, the protein expression level of integrin α5β1 increased compared with that in age-matched controls. The mice given ATN-161 had significantly reduced retinal neovascularization (RNV) and CNV. Blocking integrin a5b1 by ATN-161 strongly inhibited nuclear factor-κB (NF-κB) activation and matrix metalloproteinase-2/9 (MMP-2/9) expression and promoted cell apoptosis, but the effect of ATN-161 on proliferation in CNV mice was indirect and required the inhibition of neovascularization. Inhibiting NF-κB activation by ammonium pyrrolidinedithiocarbamate (PDTC) reduced RNV and promoted cell apoptosis in ocular NV. CONCLUSIONS Blocking integrin α5β1 by ATN-161 reduced ocular NV by inhibiting MMP-2/MMP-9 expression and promoting the cell apoptosis of ocular NV.