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Plerixafor (AMD3100)

现货
Catalog No.
A2025
趋化因子受体CXCR4拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL Ethanol)
¥ 500.00
现货
25mg
¥ 1,050.00
现货
50mg
¥ 1,880.00
现货
100mg
¥ 3,660.00
现货

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Background

Plerixafor (AMD3100) is a small-molecule antagonist of CXCR4 and CXCL12-mediated chemotaxis with IC50 of 44 nM and 5.7 nM, respectively [1].

CXCR4 and SDF-1 are key factors in regulating cancer cell invasion and metastasis, and plerixafor can prevent the binding of SDF-1 to CXCR4 for inhibiting cancer metastasis [2]. Plerixafor interfered with CXCL12/CXCR4 mediated retention of hematopoietic stem cells in the bone marrow, and resulted in their mobilization to the blood [3]. Plerixafor amplified the release of circulating neutrophils from the oriented area in the lung, while simultaneously preventing neutrophil returned to the bone marrow [4]. Three adults with WHIM syndrome were subcutaneously injected 0.01 to 0.02 mg/kg plerixafor twice daily for 6 months, circulating leukocytes were constantly increased, and associated with fewer infections [5].

References:
[1]Zabel BA, Wang Y, Lewén S, Berahovich RD, Penfold ME, Zhang P, Powers J, Summers BC, Miao Z, Zhao B, Jalili A, Janowska-Wieczorek A, Jaen JC, Schall TJ. Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J Immunol. 2009 Sep 1;183(5):3204-11.
[2].Li J, Oupický D. Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor.Biomaterials. 2014 Jul;35(21):5572-9.
[3]. Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008 Jan;15(1):49-58.
[4]. Devi S, Wang Y, Chew WK, Lima R, A-González N, Mattar CN, Chong SZ, Schlitzer A, Bakocevic N, Chew S, Keeble JL, Goh CC, Li JL, Evrard M, Malleret B, Larbi A, Renia L, Haniffa M, Tan SM, Chan JK, Balabanian K, Nagasawa T, Bachelerie F, Hidalgo A, Ginhoux F, Kubes P, Ng LG. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. J Exp Med. 2013 Oct 21;210(11):2321-36.
[5]. McDermott DH, Liu Q, Velez D, Lopez L, Anaya-O'Brien S, Ulrick J, Kwatemaa N, Starling J, Fleisher TA, Priel DA, Merideth MA, Giuntoli RL, Evbuomwan MO, Littel P, Marquesen MM, Hilligoss D, DeCastro R, Grimes GJ, Hwang ST, Pittaluga S, Calvo KR, Stratton P, Cowen EW, Kuhns DB, Malech HL, Murphy PM. A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood. 2014 Apr 10;123(15):2308-16.

文献引用

1. van Attekum MHA, van Bruggen JAC, et al. "CD40 signaling instructs chronic lymphocytic leukemia cells to attract monocytes via the CCR2 axis." Haematologica. 2017 Dec;102(12):2069-2076. PMID:28971904
2. Li P, Deng J, et al."Blockade of hypoxia-induced CXCR4 with AMD3100 inhibits production of OA-associated catabolic mediators IL-1β and MMP-13." Mol Med Rep. 2016 Aug;14(2):1475-82. PMID:27356492

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt502.78
Cas No.110078-46-1
FormulaC28H54N8
Solubility≥25.1mg/mL in Ethanol, <1.01mg/mL in DMSO, ≥2.9mg/mL in H2O with gentle warming
Chemical Name1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane
SDFDownload SDF
Canonical SMILESC1CNCCNCCCN(CCNC1)CC2=CC=C(C=C2)CN3CCCNCCNCCCNCC3
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

激酶实验 [1]:

受体结合实验

对于CXCR4的竞争性结合研究,使用Milipore DuraporeTM滤板,将不同浓度的Plerixafor与5 × 105 CCRF-CEM细胞和100 pM 125I-SDF-1α(2200 Ci/mmol)置于结合缓冲液(PBS包含5 mM MgCl2,1 mM Ca Cl2,0.25% BSA, pH 7.4)中,4°C孵育3小时。使用冷的HEPES(50 mM)和NaCl(0.5 M,pH 7.4)洗涤除去未结合的125I-SDF-1α。BLT1的竞争性结合试验于CHO-S细胞膜(表达重组BLT1)上进行。首先进行机械性剪切破坏,随后通过高速离心分离细胞裂解液,将制备所得的细胞膜重新悬浮于含50 mm HEPES和5 mM MgCl2的缓冲液中,并将其急速冷冻。在室温下,将细胞膜与Plerixafor一起孵育1小时。上述混合物包含了50 mM Tris,10 mM MgCl2(pH 7.4),10 mM CaCl2,4 nM LTB4以及1 nM 3H-LTB4(195.0 Ci/mmol)和8 μg细胞膜。使用Millipore型GF-C过滤板将未结合的3H-LTB4过滤分离。

细胞实验 [2]:

细胞系

表达EGFP-CXCR4的U2OS细胞

制备方法

在DMSO中的溶解度受限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

2.5 mg/mL;30分钟

试验结果

CXCR4和SDF-1在调节癌细胞侵袭与转移中发挥重要作用。Plerixafor有效抑制SDF-1与CXCR4结合,从而抑制癌症转移。

动物实验 [3]:

动物模型

节段性骨缺损的C57BL/6小鼠

给药剂量

5 mg/kg;腹腔注射

实验结果

给予同类小鼠PBS、IGF1、PDGF、SCF或VEGF,持续5天,在第5天给予Plerixafor。与PDGF,SCF和VEGF结合Plerixafor的试验组相比,同时接受了IGF1和Plerixafor的小鼠具有最高的菌落数量与大小。

其他注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Fricker SP, Anastassov V, Cox J, Darkes MC, Grujic O, Idzan SR, Labrecque J, Lau G, Mosi RM, Nelson KL, Qin L, Santucci Z, Wong RS. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the G-protein coupled chemokine receptor, CXCR4. Biochem Pharmacol. 2006 Aug 28;72(5):588-96.

[2]. Li J, Oupick? D. Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor.Biomaterials. 2014 Jul;35(21):5572-9.

[3]. Kumar S, Ponnazhagan S. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect. Bone. 2012 Apr;50(4):1012-8.

质量控制

化学结构

Plerixafor (AMD3100)

相关生物数据

Plerixafor (AMD3100)

相关生物数据

Plerixafor (AMD3100)