title: CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research.
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.
authors: Center for Genetic Engineering and Biotechnology, Havana, Cuba. silvio.perea@cigb.edu.cu
authors: Silvio E
authors: SE
authors: Perea
authors: Idania
authors: I
authors: Baladron
authors: Yanelda
authors: Y
authors: Garcia
authors: Yasser
authors: Y
authors: Perera
authors: Adlin
authors: A
authors: Lopez
authors: Jorge L
authors: JL
authors: Soriano
authors: Noyde
authors: N
authors: Batista
authors: Aley
authors: A
authors: Palau
authors: Ignacio
authors: I
authors: Hernández
authors: Hernán
authors: H
authors: Farina
authors: Idrian
authors: I
authors: Garcia
authors: Lidia
authors: L
authors: Gonzalez
authors: Jeovanis
authors: J
authors: Gil
authors: Arielis
authors: A
authors: Rodriguez
authors: Margarita
authors: M
authors: Solares
authors: Agueda
authors: A
authors: Santana
authors: Marisol
authors: M
authors: Cruz
authors: Matilde
authors: M
authors: Lopez
authors: Carmen
authors: C
authors: Valenzuela
authors: Osvaldo
authors: O
authors: Reyes
authors: Pedro A
authors: PA
authors: López-Saura
authors: Carlos A
authors: CA
authors: González
authors: Alina
authors: A
authors: Diaz
authors: Lila
authors: L
authors: Castellanos
authors: Aniel
authors: A
authors: Sanchez
authors: Lazaro
authors: L
authors: Betancourt
authors: Vladimir
authors: V
authors: Besada
authors: Luis J
authors: LJ
authors: González
authors: Hilda
authors: H
authors: Garay
authors: Roberto
authors: R
authors: Gómez
authors: Daniel E
authors: DE
authors: Gómez
authors: Daniel F
authors: DF
authors: Alonso
authors: Phillipe
authors: P
authors: Perrin
authors: Jean-Yves
authors: JY
authors: Renualt
authors: Hugo
authors: H
authors: Sigman
authors: Luis
authors: L
authors: Herrera
authors: Boris
authors: B
authors: Acevedo
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D057170:Translational Research, Biomedical
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D000090243:Nucleophosmin; D047390:Casein Kinase II; C532510:CIGB-300