CXCR4 Antagonists: A Screening Strategy for Identification of Functionally Selective Ligands

Journal of Biomolecular Screening

Volumn 19, Issue 6, 2014, Pages 859-869

  Castaldo, C ^a   Benicchi, T ^a,c   Otrocka, M ^b   Mori, E ^a,d   Pilli, E ^a   Ferruzzi, P ^a   Valensin, S ^a   Diamanti, D ^a   Fecke, W ^c   Varrone, M ^a,e   Porcari, V ^a  

^a Siena Biotech SpA   (Italy)

^b KAROLINSKA INSTITUTE   (Sweden)

^c TES Pharma Srl   (Italy)

^d NOVARTIS VACCINES AND DIAGNOSTICS   (Italy)

^e GLAXOSMITHKLINE   (Singapore)

Author keywords

AMD3100; biased antagonism; CXC chemokine receptor 4 (CXCR4); cyclic adenosine monophosphate (cAMP); G protein coupled receptor (GPCR); glioblastoma multiforme (GBM); high content screening (HCS); homogeneous time resolved fluorescence (HTRF); receptor internalization; arrestin

Indexed keywords

BETA ARRESTIN; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; CTCE 9908; CYCLIC AMP; FC 131; PHORBOL 13 ACETATE 12 MYRISTATE; PLERIXAFOR; T 140; UNCLASSIFIED DRUG; BETA GALACTOSIDASE; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; LIGAND; CXCL12 PROTEIN, HUMAN; CXCR4 PROTEIN, HUMAN; MOLECULAR LIBRARY; PEPTIDE; RECOMBINANT PROTEIN; RETINA S ANTIGEN; STROMAL CELL DERIVED FACTOR 1;

ANIMAL CELL; ARTICLE; CAMP ASSAY; CHO CELL LINE; CONTROLLED STUDY; DRUG SCREENING; FLUORESCENCE ACTIVATED CELL SORTING; GLIOBLASTOMA CELL LINE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; INTERNALIZATION; MODULATION; MOLECULAR LIBRARY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR INTERNALIZATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; U2OS CELL LINE; CONCENTRATION RESPONSE; DRUG POTENCY; ENZYME FRAGMENT COMPLEMENTATION ASSAY; HIGH CONTENT SCREENING; HOMOGENEOUS TIME RESOLVED FLUORESCENCE; SCREENING TEST; VALIDATION PROCESS; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CELL SEPARATION; CHEMISTRY; CRICETULUS; DISEASE COURSE; FLOW CYTOMETRY; HAMSTER; MASS SCREENING; PHOSPHORYLATION; SPECTROFLUOROMETRY; TUMOR CELL LINE;

ANIMALS; ARRESTINS; BETA-ARRESTINS; BETA-GALACTOSIDASE; CELL LINE; CELL LINE, TUMOR; CELL SEPARATION; CHEMOKINE CXCL12; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; DISEASE PROGRESSION; FLOW CYTOMETRY; HUMANS; LIGANDS; MASS SCREENING; PEPTIDES; PHOSPHORYLATION; RECEPTORS, CXCR4; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; SPECTROMETRY, FLUORESCENCE;

EID: 84904902909     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057114526283     Document Type: Article

References (30)

1. Ganju R. K., Brubaker S. A., Meyer J., et al. The α-Chemokine, Stromal Cell-Derived Factor-1α Binds to the Transmembrane G-Protein-Coupled CXCR-4 Receptor and Activates Multiple Signal Transduction Pathways. J. Biol. Chem. 1998 ; 273 (36). 23169-23175 (Pubitemid 28417500)
2. Cojoc M., Peitzsch C., Trautmann F., et al. Emerging Targets in Cancer Management: Role of the CXCL12/CXCR4 Axis. Onco. Targets Ther. 2013 ; 6: 1347-1361
3. Nagasawa T., Tachibana K., Kishimoto T.. A Novel CXC Chemokine PBSF/SDF-1 and Its Receptor CXCR4: Their Functions in Development, Hematopoiesis and HIV Infection. Sem. Immunol. 1998 ; 10 (3). 179-185 (Pubitemid 28347034)
4. Diaz G. A., Gulino A. V.. WHIM Syndrome: A Defect in CXCR4 Signaling. Curr. Allergy Asthma Rep. 2005 ; 5 (5). 350-355 (Pubitemid 41683977)
5. Li M., Ransohoff R. M.. Multiple Roles of Chemokine CXCL12 in the Central Nervous System: A Migration from Immunology to Neurobiology. Prog. Neurobiol. 2008 ; 84 (2). 116-131
6. Ehtesham M., Min E., Issar N. M., et al. The Role of the CXCR4 Cell Surface Chemokine Receptor in Glioma Biology. J. Neurooncol. 2013 ; 113 (2). 153-162
7. Guleng B., Tateishi K., Ohta M., et al. Blockade of the Stromal Cell-Derived Factor-1/CXCR4 Axis Attenuates in Vivo Tumor Growth by Inhibiting Angiogenesis in a Vascular Endothelial Growth Factor-Independent Manner. Cancer Res. 2005 ; 65: 5864-5871 (Pubitemid 40911192)
8. Rubin J. B.. Chemokine Signaling in Cancer: One Hump or Two?. Semin. Cancer Biol. 2009 ; 19: 116-122
9. Yang L., Jackson E., Woerner B. M., et al. Blocking CXCR4-Mediated Cyclic AMP Suppression Inhibits Brain Tumor Growth in Vivo. Cancer Res. 2007 ; 67 (2). 651-658 (Pubitemid 46192204)
10. Holland J. D., Kochetkova M., Akekawatchai C., et al. Different functional activation of chemokine receptor CXCR4 is mediated by G proteins in breast cancer cells. Cancer Res. 2006 ; 6 (8). 4117-4124
11. Klein R., Rubin J. B., Gibson H. D., et al. SDF-1a Induces Chemotaxis and Enhances Sonic Hedgehog-Induced Proliferation of Cerebellar Granule Cells. Development. 2001 ; 128: 1971-1981 (Pubitemid 32600461)
12. Luttrell L. M., Lefkowitz R. J.. The Role of Beta-Arrestins in the Termination and Transduction of G-Protein-Coupled Receptor Signals. J. Cell. Sci. 2002 ; 115: 455-465 (Pubitemid 34182973)
13. Cheng Z. J., Zhao J., Sun Y., et al. β-Arrestin Differentially Regulates the Chemokine Receptor CXCR4-Mediated Signaling and Receptor Internalization, and This Implicates Multiple Interaction Sites between β-Arrestin and CXCR4. J. Biol. Chem. 2000 ; 275 (4). 2479-2485 (Pubitemid 30082009)
14. Sun Y., Cheng Z., Ma L., et al. β-Arrestin2 Is Critically Involved in CXCR4-Mediated Chemotaxis, and This Is Mediated by Its Enhancement of p38 MAPK Activation. J. Biol. Chem. 2002 ; 277 (51). 49212-49219 (Pubitemid 36014350)
15. Gross N., Meier R.. Chemokines in Neuroectodermal Cancers: The Crucial Growth Signal from the Soil. Semin. Cancer Biol. 2009 ; 19 (2). 103-110
16. Kalatskaya I., Berchiche Y. A., Gravel S., et al. AMD3100 Is a CXCR7 Ligand with Allosteric Agonist Properties. Mol. Pharm. 2009 ; 75 (5). 1240-1247
17. Domanska U. M., Kruizinga R. C., Nagengast W. B., et al. A Review on CXCR4/CXCL12 Axis in Oncology: No Place to Hide. Eur. J. Cancer. 2013 ; (49 1). 219-230
18. Richert M. M., Vaidya K. S., Mills C. N., et al. Inhibition of CXCR4 by CTCE-9908 Inhibits Breast Cancer Metastasis to Lung and Bone. Oncol. Rep. 2005 ; 21: 761-767
19. Tamamura H., Hori A., Kanzaki N., et al. T140 Analogs as CXCR4 Antagonists Identified as Anti-Metastatic Agents in the Treatment of Breast Cancer. FEBS Lett. 2003 ; 550: 79-83 (Pubitemid 37281361)
20. Fujii N., Oishi S., Hiramatsu K., et al. Molecular-Size Reduction of a Potent CXCR4-Chemokine Antagonist Using Orthogonal Combination of Conformation- and Sequence-Based Libraries. Angew Chem. Int. Ed. Engl. 2003 ; 42 (28). 3251-3253 (Pubitemid 36917168)
21. Signoret N., Oldridge J., Pelchen-Matthews A., et al. Phorbol Esters and SDF-1 Induce Rapid Endocytosis and Down Modulation of the Chemokine Receptor CXCR4. J. Cell Biol. 1997 ; 139: 651-664 (Pubitemid 27485831)
22. SittampalamG. S.Gal-EddN.ArkinM.. Assay Guidance Manual [Online]; Eli Lilly & Company and the National Center for Advancing Translational Sciences: Bethesda, MD, 2004. http://www.ncbi.nlm.nih.gov/books/NBK53196/ (accessed Feb 25, 2014).
23. Zhang J. H., Chung T. D., Oldenburg K. R.. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J. Biom. Screen. 1999 ; 4: 67-73 (Pubitemid 29278954)
24. Eastwood B. J., Farmen M. W., Iversen P. W., et al. The Minimum Significant Ratio: A Statistical Parameter to Characterize the Reproducibility of Potency Estimates from Concentration-Response Assays and Estimation by Replicate Experiment Studies. J. Biomol. Screen. 2006 ; 11: 253-261
25. Hatse S., Princen K., Bridger G., et al. Chemokine Receptor Inhibition by AMD3100 Is Strictly Confined to CXCR4. DFEBS Lett. 2002 ; 527 (1-3). 255-262 (Pubitemid 35253875)
26. Hendrix C. W., Collier A. C., Lederman M., et al. Safety, Pharmacokinetics, and Antiviral Activity of AMD3100, a Selective CXCR4 Receptor Inhibitor, in HIV-1 Infection. J. Acquir. Immune Defic. Syndr. 2004 ; 37: 1253-1262 (Pubitemid 39281506)
27. Meier R., Mühlethaler-Mottet A., Flahaut M., et al. The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but Not Invasion. PLoS ONE. 2007 ; 2 (10). e1016
28. Orsini M. J., Parent J. L., Mundell S. J., et al. Trafficking of the HIV Coreceptor CXCR4. J. Biol. Chem. 1999 ; 274 (43). 31076-31086
29. Van Koppen C. J, Jakobs K. H.. Arrestin-Independent Internalization of G Protein Coupled Receptors. Mol. Pharmacol. 2004 ; 66: 365-367 (Pubitemid 39329234)
30. Percherancier Y., Berchiche Y. A., Slight I., et al. Bioluminescence Resonance Energy Transfer Reveals Ligand-Induced Conformational Changes in CXCR4 Homo- and Heterodimers. J. Biol. Chem. 2005 ; 280 (11). 9895-9903 (Pubitemid 40395837)