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CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

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Abstract

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.

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Abbreviations

MTD:

Maximal tolerated dose

DLT:

Dose-limiting toxicity

CIGB-300-B:

CIGB-300 conjugated to biotin

BFS:

Bovine fetal serum

TBB:

4,5,6,7-Tetrabromobenzotriazole

PBS:

Phosphate buffer solution

RIPA:

Radioimmunoprecipitation assay

HPV:

Human papillomavirus

99Tc:

Technetium-99

MRI:

Magnetic resonance images

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Acknowledgments

This study was supported by HeberBiotec SA and Biorec.

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Authors and Affiliations

  1. Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba

    Silvio E. Perea, Idania Baladron, Yanelda Garcia, Yasser Perera, Idrian Garcia, Lidia Gonzalez, Jeovanis Gil, Arielis Rodriguez, Marisol Cruz, Matilde Lopez, Carmen Valenzuela, Osvaldo Reyes, Pedro A. López-Saura, Lila Castellanos, Aniel Sanchez, Lazaro Betancourt, Vladimir Besada, Luis J. González, Hilda Garay, Luis Herrera & Boris Acevedo

  2. Gyneco-obstetric Hospital “Clodomira Acosta Ferrales”, Havana, Cuba

    Margarita Solares

  3. Gyneco-obstetric Hospital “10 de Octubre”, Havana, Cuba

    Agueda Santana

  4. National Center for Toxicology, Havana, Cuba

    Carlos A. González & Alina Diaz

  5. General Hospital “Hermanos Ameijeiras”, Havana, Cuba

    Adlin Lopez, Jorge L. Soriano, Noyde Batista & Aley Palau

  6. Isotopes Center, Havana, Cuba

    Ignacio Hernández

  7. ELEA Laboratorios, Buenos Aires, Argentina

    Roberto Gómez & Hugo Sigman

  8. National University of Quilmes, Buenos Aires, Argentina

    Hernán Farina, Daniel E. Gómez & Daniel F. Alonso

  9. Chemo Group, Paris, France

    Phillipe Perrin & Jean-Yves Renualt

Authors
  1. Silvio E. Perea
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  2. Idania Baladron
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  9. Ignacio Hernández
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  11. Idrian Garcia
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  12. Lidia Gonzalez
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  13. Jeovanis Gil
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  14. Arielis Rodriguez
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  15. Margarita Solares
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  16. Agueda Santana
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  18. Matilde Lopez
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  19. Carmen Valenzuela
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  20. Osvaldo Reyes
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  21. Pedro A. López-Saura
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  22. Carlos A. González
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  23. Alina Diaz
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  24. Lila Castellanos
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  25. Aniel Sanchez
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  26. Lazaro Betancourt
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  27. Vladimir Besada
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  28. Luis J. González
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  29. Hilda Garay
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  30. Roberto Gómez
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  31. Daniel E. Gómez
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  32. Daniel F. Alonso
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  33. Phillipe Perrin
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  34. Jean-Yves Renualt
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  35. Hugo Sigman
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  36. Luis Herrera
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  37. Boris Acevedo
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Corresponding author

Correspondence to Silvio E. Perea.

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Perea, S.E., Baladron, I., Garcia, Y. et al. CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research. Mol Cell Biochem 356, 45–50 (2011). https://doi.org/10.1007/s11010-011-0950-y

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  • DOI: https://doi.org/10.1007/s11010-011-0950-y

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