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AMD-070

现货
Catalog No.
A3173
CXCR4拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,800.00
现货
5mg
¥ 1,680.00
现货
10mg
¥ 3,000.00
现货
25mg
¥ 6,380.00
现货
50mg
¥ 10,200.00
现货

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Background

AMD-070 is a selective and oral bioavailable antagonist of chemokine receptor CXCR4 with IC50 value of 13 nM [1].
CXCR4 is a G-protein-coupled receptor that plays important roles in tumor development. It affects the migration, proliferation and survival of cancer cells through the CXCL12-mediated MAPK signaling. AMD-070 is an orally bioavailable antagonist of CXCR4 and is found to be an inhibitor of tumor cell migration. CXCR4 is also one of the two chemokine receptors that are used by virus for infecting human cells. As a CXCR4 inhibitor, AMD-070 can repress the replication of X4 (T-tropic) HIV-1 and the interaction of gp120/CXCR4 potently. The mechanistic studies demonstrate that AMD-070 is an allosteric inhibitor. It was found that a hydrogen bond was formed between the benzimidazole of AMD-070 and the Tyr45 residue of CXCR4 whereas the residues Asp262, Asp171 and Glu288 were not involved in the direct interactions with AMD-070 [1, 2 and 3].
AMD-070 is selective against CXCR4 over other related G-protein-coupled chemokine receptors including CXCR1, CXCR2, CCR1, CCR2b, CCR4 and CCR5. The IC50 values of AMD-070 against these GPCRs were all above 10 μM. In HOS cells expressing human CXCR4, AMD-070 inhibited HIV-1 infection with IC50 value of 10 nM. In CD4+CXCR4+T cells, AMD-070 showed anti-HIV-1 activity (IC50 value of 2 nM) through inhibiting the SDF-1 induced calcium flux with IC50 value of 12 nM. In addition, AMD-070 inhibited the competitive binding of 125I-SDF-1with IC50 value of 13 nM. In melanoma cells CHL-1 and A375, treatment of AMD-070 significantly inhibited the migration of cells. Besides that, the void sizes of cells were also increased by the inhibitor treatment [1, 2 and 4].
References:
[1] Skerlj RT, Bridger GJ, Kaller A, McEachern EJ, Crawford JB, Zhou Y, Atsma B, Langille J, Nan S, Veale D, Wilson T, Harwig C, Hatse S, Princen K, De Clercq E, Schols D. Discovery of novel small molecule orally bioavailable C-X-C chemokine receptor 4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication. J Med Chem. 2010 Apr 22;53(8):3376-88.
[2] O'Boyle G, Swidenbank I, Marshall H, Barker CE, Armstrong J, White SA, Fricker SP, Plummer R, Wright M, Lovat PE. Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070. Br J Cancer. 2013 Apr 30;108(8):1634-40.
[3] Wong RS, Bodart V, Metz M, Labrecque J, Bridger G, Fricker SP. Comparison of the potential multiple binding modes of bicyclam, monocylam, and noncyclam small-molecule CXC chemokine receptor 4 inhibitors. Mol Pharmacol. 2008 Dec;74(6):1485-95.
[4] Gudmundsson KS, Sebahar PR, Richardson LD, Miller JF, Turner EM, Catalano JG, Spaltenstein A, Lawrence W, Thomson M, Jenkinson S. Amine substituted  N-(1H-benzimidazol-2ylmethyl)-5,6,7,8-tetrahydro-8-quinolinamines as CXCR4 antagonists with potent activity against HIV-1. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5048-52.

Chemical Properties

Physical AppearanceA brown oil
StorageStore at -20°C
M.Wt349.48
Cas No.558447-26-0
FormulaC21H27N5
SynonymsAMD 070; AMD070
Solubility≥17.45 mg/mL in DMSO, ≥44.5 mg/mL in EtOH, ≥7.47 mg/mL in H2O with gentle warming
Chemical NameN'-(1H-benzimidazol-2-ylmethyl)-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
SDFDownload SDF
Canonical SMILESC1CC(C2=C(C1)C=CC=N2)N(CCCCN)CC3=NC4=CC=CC=C4N3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1,2]:

细胞系

黑色素瘤细胞系CHL-1和A375, HOS细胞

溶解方法

该化合物在DMSO中的溶解度大于17.5mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

6.6 μM, 24h

应用

在黑色素瘤细胞CHL-1和A375中,AMD-070的治疗显著抑制细胞迁移。此外,抑制剂处理也增加了细胞的空隙大小。在表达人CXCR4的HOS细胞中,AMD-070抑制HIV-1感染,IC50值为10 nM。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1] O'boyle G, Swidenbank I, Marshall H, et al. Inhibition of CXCR4–CXCL12 chemotaxis in melanoma by AMD11070[J]. British journal of cancer, 2013, 108(8): 1634.

[2] Gudmundsson K S, Sebahar P R, Richardson L D A, et al. Amine substituted N-(1H-benzimidazol-2ylmethyl)-5, 6, 7, 8-tetrahydro-8-quinolinamines as CXCR4 antagonists with potent activity against HIV-1[J]. Bioorganic & medicinal chemistry letters, 2009, 19(17): 5048-5052.

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