UniPR129 is a competitive small molecule Eph-ephrin antagonist blocking in vitro angiogenesis at low micromolar concentrations

British Journal of Pharmacology

Volumn 171, Issue 23, 2014, Pages 5195-5208

  Hassan Mohamed, I ^a   Giorgio, C ^a   Incerti, M ^a   Russo, S ^a   Pala, D ^a   Pasquale, E B ^b   Zanotti, I ^a   Vicini, P ^a   Barocelli, E ^a   Rivara, S ^a   Mor, M ^a   Lodola, A ^a   Tognolini, M ^a  

^a UNIVERSITY OF PARMA   (Italy)

^b BURNHAM INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DASATINIB; EPHRIN A1; EPHRIN RECEPTOR A2; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; UNIPR 129; VASCULOTROPIN RECEPTOR 2; ANGIOGENESIS INHIBITOR; EPHRIN RECEPTOR B4; LITHOCHOLIC ACID; TRYPTOPHAN; UNIPR129; VASCULOTROPIN RECEPTOR;

ADENOCARCINOMA CELL LINE; APOPTOSIS; ARTICLE; BINDING ASSAY; CELL CYCLE; CELL MIGRATION; CELL PROLIFERATION; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; LIGAND BINDING; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROSTATE ADENOCARCINOMA; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; ANALOGS AND DERIVATIVES; ANGIOGENESIS; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; METABOLISM; MOLECULAR DOCKING; PHYSIOLOGY; TUMOR CELL LINE; UMBILICAL VEIN ENDOTHELIAL CELL;

ANGIOGENESIS INHIBITORS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; EPHRIN-A1; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; LITHOCHOLIC ACID; MOLECULAR DOCKING SIMULATION; NEOVASCULARIZATION, PHYSIOLOGIC; RECEPTOR, EPHA2; RECEPTOR, EPHB4; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; TRYPTOPHAN;

EID: 84925862007     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12669     Document Type: Article

References (47)

1. Abéngozar MA, Frutos S, de Ferreiro S, Soriano J, Perez-Martinez M, Olmeda D, et al. (2012). Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth. Blood 119: 4565-4576.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al (2013). The Concise Guide to PHARMACOLOGY 2013/14: Catalytic Receptors. Br J Pharmacol 170: 1676-1705.
3. Arunlakshana O, Schild HO, (1959). Some quantitative uses of drug antagonists. Br J Pharmacol Chemother 14: 48-58.
4. Baell JB, Holloway GA, (2010). New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 53: 2719-2740.
5. Binda E, Visioli A, Giani F, Lamorte G, Copetti M, Pitter KL, et al. (2012). The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas. Cancer Cell 22: 765-780.
6. Cheng N, Brantley DM, Liu H, Lin Q, Enriquez M, Gale N, et al. (2002). Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res 1: 2-11.
7. Chrencik JE, Brooun A, Kraus ML, Recht MI, Kolatkar AR, Han GW, et al. (2006). Structural and biophysical characterization of the EphB4-ephrinB2 protein-protein interaction and receptor specificity. J Biol Chem 281: 28185-28192.
8. Ferrara N, Hillan KJ, Novotny W, (2005). Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333: 328-335.
9. Giorgio C, Hassan Mohamed I, Flammini L, Barocelli E, Incerti M, Lodola A, et al. (2011). Lithocholic acid is an Eph-ephrin ligand interfering with Eph-kinase activation. PLoS ONE 6: e18128.
10. Guimarães CRW, Cardozo M, (2008). MM-GB/SA rescoring of docking poses in structure-based lead optimization. J Chem Inf Model 48: 958-970.
11. Héroult M, Schaffner F, Augustin HG, (2006). Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Exp Cell Res 312: 642-650.
12. Himanen J-P, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD, et al. (2004). Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci 7: 501-509.
13. Himanen JP, Goldgur Y, Miao H, Myshkin E, Guo H, Buck M, et al. (2009). Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex. EMBO Rep 10: 722-728.
14. Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, et al. (2010). Architecture of Eph receptor clusters. Proc Natl Acad Sci U S A 107: 10860-10865.
15. Huang X, Wu D, Jin H, Stupack D, Wang JYJ, (2008). Induction of cell retraction by the combined actions of Abl-CrkII and Rho-ROCK1 signaling. J Cell Biol 183: 711-723.
16. Incerti M, Tognolini M, Russo S, Pala D, Giorgio C, Hassan-Mohamed I, et al. (2013). Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem 56: 2936-2947.
17. Jehle J, Staudacher I, Wiedmann F, Schweizer P, Becker R, Katus H, et al. (2012). Regulation of apoptosis in HL-1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid. Br J Pharmacol 167: 1563-1572.
18. Jorgensen WL, Maxwell DS, Tirado-Rives J, (1996). Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118: 11225-11236.
19. Jubb AM, Harris AL, (2010). Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol 11: 1172-1183.
20. Konstantinova I, Nikolova G, Ohara-Imaizumi M, Meda P, Kucera T, Zarbalis K, et al. (2007). EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell 129: 359-370.
21. Lafleur K, Huang D, Zhou T, Caflisch A, Nevado C, (2009). Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem 52: 6433-6446.
22. van Linden OPJ, Farenc C, Zoutman WH, Hameetman L, Wijtmans M, Leurs R, et al. (2012). Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase. Eur J Med Chem 47: 493-500.
23. Martiny-Baron G, Holzer P, Billy E, Schnell C, Brueggen J, Ferretti M, et al. (2010). The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis. Angiogenesis 13: 259-267.
24. Mellitzer G, Xu Q, Wilkinson DG, (1999). Eph receptors and ephrins restrict cell intermingling and communication. Nature 400: 77-81.
25. Miao H, Burnett E, Kinch M, Simon E, Wang B, (2000). Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol 2: 62-69.
26. Mohamed IH, Giorgio C, Bruni R, Flammini L, Barocelli E, Rossi D, et al. (2011). Polyphenol rich botanicals used as food supplements interfere with EphA2-ephrinA1 system. Pharmacol Res 64: 464-470.
27. Noberini R, Koolpe M, Peddibhotla S, Dahl R, Su Y, Cosford NDP, et al. (2008). Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2 receptors. J Biol Chem 283: 29461-29472.
28. Noberini R, De SK, Zhang Z, Wu B, Raveendra-Panickar D, Chen V, et al. (2011). A disalicylic acid-furanyl derivative inhibits ephrin binding to a subset of Eph receptors. Chem Biol Drug Des 78: 667-678.
29. Noberini R, Koolpe M, Lamberto I, Pasquale EB, (2012a). Inhibition of Eph receptor-ephrin ligand interaction by tea polyphenols. Pharmacol Res 66: 363-373.
30. Noberini R, Lamberto I, Pasquale EB, (2012b). Targeting Eph receptors with peptides and small molecules: progress and challenges. Semin Cell Dev Biol 23: 51-57.
31. Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, et al. (2009). Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15: 220-231.
32. Parrinello S, Napoli I, Ribeiro S, Wingfield Digby P, Fedorova M, Parkinson DB, et al. (2010). EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. Cell 143: 145-155.
33. Pasquale EB, (1997). The Eph family of receptors. Curr Opin Cell Biol 9: 608-615.
34. Pasquale EB, (2005). Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6: 462-475.
35. Pasquale EB, (2010). Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 10: 165-180.
36. Petty A, Myshkin E, Qin H, Guo H, Miao H, Tochtrop GP, et al. (2012). A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo. PLoS ONE 7: e42120.
37. Prevost N, Woulfe D, Tognolini M, Brass LF, (2003). Contact-dependent signaling during the late events of platelet activation. J Thromb Haemost 1: 1613-1627.
38. Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, et al. (2010). Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465: 487-491.
39. Sebolt-Leopold JS, English JM, (2006). Mechanisms of drug inhibition of signalling molecules. Nature 441: 457-462.
40. Tandon M, Vemula SV, Mittal SK, (2011). Emerging strategies for EphA2 receptor targeting for cancer therapeutics. Expert Opin Ther Targets 15: 31-51.
41. Tognolini M, Giorgio C, Hassan Mohamed I, Barocelli E, Calani L, Reynaud E, et al. (2012a). Perturbation of the EphA2-EphrinA1 system in human prostate cancer cells by colonic (poly)phenol catabolites. J Agric Food Chem 60: 8877-8884.
42. Tognolini M, Incerti M, Hassan-Mohamed I, Giorgio C, Russo S, Bruni R, et al. (2012b). Structure-activity relationships and mechanism of action of Eph-ephrin antagonists: interaction of cholanic acid with the EphA2 receptor. ChemMedChem 7: 1071-1083.
43. Tognolini M, Hassan-Mohamed I, Giorgio C, Zanotti I, Lodola A, (2013a). Therapeutic perspectives of Eph-ephrin system modulation. Drug Discov Today. doi: 10.1016/j.drudis.2013.11.017.
44. Tognolini M, Incerti M, Pala D, Russo S, Castelli R, Hassan-Mohamed I, et al. (2013b). Target hopping as a useful tool for the identification of novel EphA2 protein-protein antagonists. ChemMedChem 9: 67-72.
45. Van Hoecke A, Schoonaert L, Lemmens R, Timmers M, Staats KA, Laird AS, et al. (2012). EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat Med 18: 1418-1422.
46. Wu B, Zhang Z, Noberini R, Barile E, Giulianotti M, Pinilla C, et al. (2013). HTS by NMR of combinatorial libraries: a fragment-based approach to ligand discovery. Chem Biol 20: 19-33.
47. Xu Q, Mellitzer G, Robinson V, Wilkinson DG, (1999). In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399: 267-271.