An antagonist of CXCR4
Plerixafor 8HCl (AMD3100 8HCl) is a potent and selective antagonist of CXCL12-mediated chemotaxis and G-protein coupled chemokine receptor (CXCR4) with IC50 values of 5.7 and 44 nM, respectively [1]. Plerixafor 8HCl has shown a high selectivity for CXCR4 compared other chemokine receptors including LTB4 CCR1, CCR2b, CCR4, CCR5, CCR7, CXCR3, etc [2].
Plerixafor 8HCl showed to inhibit I-SDF-1 ligand binding to CCRF–CEM T-lymphoblastoid cells which express CXCR4. Plerixafor 8HCl has shown to block CXCR4 activation, SDF-1 mediated calcium flux and SDF-1 mediated chemotaxis with IC50 values of 27.3, 572 and 51 nM, respectively [2].
参考文献:
[1] Zabel BA1,?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. doi: 10.4049/jimmunol.0900269. Epub 2009 Jul 29.
[2] Fricker SP1,?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?coupledchemokine?receptor,?CXCR4. Biochem Pharmacol.?2006 Aug 28;72(5):588-96.
| Cell experiment [1]: | |
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Cell lines |
Bone marrow mononuclear cells (BMMCs) |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM |
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Applications |
In BMMCs, AMD3100 neutralizes the osteoclast formation promoted by SDF-1α. AMD3100 could also diminish the expression of osteoclast-specific proteins elevated by SDF-1α. |
| Animal experiment [2]: | |
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Animal models |
8-10 week-old specified pathogen-free female C57BL/6 mice |
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Dosage form |
3 mg/kg daily, i.p. |
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Application |
Administration of the CXCR4 antagonist AMD3100 reduced the uptake of tracer that specifically binding to interleukin-2 receptors expressed on activated CD25+ T cells by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes in cancer treatment. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Dong Y, Liu H, Zhang X, et al. Inhibition of SDF-1α/CXCR4 signalling in subchondral bone attenuates post-traumatic osteoarthritis[J]. International Journal of Molecular Sciences, 2016, 17(6): 943. [2]. Hartimath S V, Draghiciu O, van de Wall S, et al. Noninvasive monitoring of cancer therapy induced activated T cells using [18F] FB-IL-2 PET imaging[J]. OncoImmunology, 2017, 6(1): e1248014. |
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