---
res:
  bibo_abstract:
  - Vaccinia-related kinase 1 (VRK1) and the δ and ε isoforms of casein kinase 1 (CK1)
    are linked to various disease-relevant pathways. However, the lack of tool compounds
    for these kinases has significantly hampered our understanding of their cellular
    functions and therapeutic potential. Here, we describe the structure-based development
    of potent inhibitors of VRK1, a kinase highly expressed in various tumor types
    and crucial for cell proliferation and genome integrity. Kinome-wide profiling
    revealed that our compounds also inhibit CK1δ and CK1ε. We demonstrate that dihydropteridinones
    35 and 36 mimic the cellular outcomes of VRK1 depletion. Complementary studies
    with existing CK1δ and CK1ε inhibitors suggest that these kinases may play overlapping
    roles in cell proliferation and genome instability. Together, our findings highlight
    the potential of VRK1 inhibition in treating p53-deficient tumors and possibly
    enhancing the efficacy of existing cancer therapies that target DNA stability
    or cell division.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Fernando H.
      foaf_name: de Souza Gama, Fernando H.
      foaf_surname: de Souza Gama
  - foaf_Person:
      foaf_givenName: Luiz A.
      foaf_name: Dutra, Luiz A.
      foaf_surname: Dutra
  - foaf_Person:
      foaf_givenName: Michael
      foaf_name: Hawgood, Michael
      foaf_surname: Hawgood
  - foaf_Person:
      foaf_givenName: Caio Vinícius
      foaf_name: dos Reis, Caio Vinícius
      foaf_surname: dos Reis
  - foaf_Person:
      foaf_givenName: Ricardo A. M.
      foaf_name: Serafim, Ricardo A. M.
      foaf_surname: Serafim
  - foaf_Person:
      foaf_givenName: Marcos A.
      foaf_name: Ferreira, Marcos A.
      foaf_surname: Ferreira
  - foaf_Person:
      foaf_givenName: Bruno V. M.
      foaf_name: Teodoro, Bruno V. M.
      foaf_surname: Teodoro
  - foaf_Person:
      foaf_givenName: Jéssica Emi
      foaf_name: Takarada, Jéssica Emi
      foaf_surname: Takarada
  - foaf_Person:
      foaf_givenName: André S.
      foaf_name: Santiago, André S.
      foaf_surname: Santiago
  - foaf_Person:
      foaf_givenName: Dimitrios-Ilias
      foaf_name: Balourdas, Dimitrios-Ilias
      foaf_surname: Balourdas
  - foaf_Person:
      foaf_givenName: Ann-Sofie
      foaf_name: Nilsson, Ann-Sofie
      foaf_surname: Nilsson
  - foaf_Person:
      foaf_givenName: Bruno
      foaf_name: Urien, Bruno
      foaf_surname: Urien
  - foaf_Person:
      foaf_givenName: Vitor M.
      foaf_name: Almeida, Vitor M.
      foaf_surname: Almeida
  - foaf_Person:
      foaf_givenName: Carina
      foaf_name: Gileadi, Carina
      foaf_surname: Gileadi
  - foaf_Person:
      foaf_givenName: Priscila Z.
      foaf_name: Ramos, Priscila Z.
      foaf_surname: Ramos
  - foaf_Person:
      foaf_givenName: Anita P
      foaf_name: Testa Salmazo, Anita P
      foaf_surname: Testa Salmazo
      foaf_workInfoHomepage: http://www.librecat.org/personId=41F1F098-F248-11E8-B48F-1D18A9856A87
  - foaf_Person:
      foaf_givenName: Stanley N. S.
      foaf_name: Vasconcelos, Stanley N. S.
      foaf_surname: Vasconcelos
  - foaf_Person:
      foaf_givenName: Micael R.
      foaf_name: Cunha, Micael R.
      foaf_surname: Cunha
  - foaf_Person:
      foaf_givenName: Susanne
      foaf_name: Mueller, Susanne
      foaf_surname: Mueller
  - foaf_Person:
      foaf_givenName: Stefan
      foaf_name: Knapp, Stefan
      foaf_surname: Knapp
  - foaf_Person:
      foaf_givenName: Katlin B.
      foaf_name: Massirer, Katlin B.
      foaf_surname: Massirer
  - foaf_Person:
      foaf_givenName: Jonathan M.
      foaf_name: Elkins, Jonathan M.
      foaf_surname: Elkins
  - foaf_Person:
      foaf_givenName: Opher
      foaf_name: Gileadi, Opher
      foaf_surname: Gileadi
  - foaf_Person:
      foaf_givenName: Alessandra
      foaf_name: Mascarello, Alessandra
      foaf_surname: Mascarello
  - foaf_Person:
      foaf_givenName: Bennie B. L. G.
      foaf_name: Lemmens, Bennie B. L. G.
      foaf_surname: Lemmens
  - foaf_Person:
      foaf_givenName: Cristiano R. W.
      foaf_name: Guimarães, Cristiano R. W.
      foaf_surname: Guimarães
  - foaf_Person:
      foaf_givenName: Hatylas
      foaf_name: Azevedo, Hatylas
      foaf_surname: Azevedo
  - foaf_Person:
      foaf_givenName: Rafael M.
      foaf_name: Couñago, Rafael M.
      foaf_surname: Couñago
  bibo_doi: 10.1021/acs.jmedchem.3c02250
  bibo_issue: '11'
  bibo_volume: 67
  dct_date: 2024^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/0022-2623
  - http://id.crossref.org/issn/1520-4804
  dct_language: eng
  dct_publisher: American Chemical Society@
  dct_title: Novel dihydropteridinone derivatives as potent inhibitors of the understudied
    human kinases vaccinia-related kinase 1 and casein kinase 1δ/ε@
  fabio_hasPubmedId: '38780468'
...