AMD-070 (Synonyms: AMD 070, AMD 11070, X4P-001) |
| カタログ番号GC12196 |
CXCR4拮抗剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 558447-26-0
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1,2]: | |
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Cell lines |
Melanoma cells CHL-1 and A375, HOS cells |
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Preparation method |
The solubility of this compound in DMSO is >17.5mg/mL. 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. |
|
Reacting condition |
6.6 μM, 24h |
|
Applications |
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. In HOS cells expressing human CXCR4, AMD-070 inhibited HIV-1 infection with IC50 value of 10 nM. |
|
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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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. | |
| Cas No. | 558447-26-0 | SDF | |
| 同義語 | AMD 070, AMD 11070, X4P-001 | ||
| Chemical Name | N'-(1H-benzimidazol-2-ylmethyl)-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine | ||
| Canonical SMILES | C1CC(C2=C(C1)C=CC=N2)N(CCCCN)CC3=NC4=CC=CC=C4N3 | ||
| Formula | C21H27N5 | M.Wt | 349.48 |
| 溶解度 | ≥ 17.45 mg/mL in DMSO, ≥ 44.5 mg/mL in EtOH, ≥ 7.47 mg/mL in Water with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8614 mL | 14.307 mL | 28.6139 mL |
| 5 mM | 0.5723 mL | 2.8614 mL | 5.7228 mL |
| 10 mM | 0.2861 mL | 1.4307 mL | 2.8614 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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