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@ARTICLE{Grygier:600080,
      author       = {Grygier, Przemyslaw and Pustelny, Katarzyna and Nowak,
                      Jakub and Golik, Przemyslaw and Popowicz, Grzegorz M. and
                      Plettenburg, Oliver and Dubin, Grzegorz and Menezes, Filipe
                      and Czarna, Anna},
      title        = {{S}ilmitasertib ({CX}-4945), a {C}linically {U}sed
                      {CK}2-{K}inase {I}nhibitor with {A}dditional {E}ffects on
                      {GSK}3β and {DYRK}1{A} {K}inases: {A} {S}tructural
                      {P}erspective},
      journal      = {Journal of medicinal chemistry},
      volume       = {66},
      number       = {6},
      issn         = {0095-9065},
      address      = {Washington, DC},
      publisher    = {ACS},
      reportid     = {PUBDB-2023-07733},
      pages        = {4009 - 4024},
      year         = {2023},
      abstract     = {A clinical casein kinase 2 inhibitor, CX-4945
                      (silmitasertib), shows significant affinity toward the
                      DYRK1A and GSK3β kinases, involved in down syndrome
                      phenotypes, Alzheimer’s disease, circadian clock
                      regulation, and diabetes. This off-target activity offers an
                      opportunity for studying the effect of the DYRK1A/GSK3β
                      kinase system in disease biology and possible line
                      extension. Motivated by the dual inhibition of these
                      kinases, we solved and analyzed the crystal structures of
                      DYRK1A and GSK3β with CX-4945. We built a
                      quantum-chemistry-based model to rationalize the compound
                      affinity for CK2α, DYRK1A, and GSK3β kinases. Our
                      calculations identified a key element for CK2α’s
                      subnanomolar affinity to CX-4945. The methodology is
                      expandable to other kinase selectivity modeling. We show
                      that the inhibitor limits DYRK1A- and GSK3β-mediated cyclin
                      D1 phosphorylation and reduces kinase-mediated NFAT
                      signaling in the cell. Given the CX-4945’s clinical and
                      pharmacological profile, this inhibitory activity makes it
                      an interesting candidate with potential for application in
                      additional disease areas.},
      cin          = {DOOR ; HAS-User},
      ddc          = {610},
      cid          = {I:(DE-H253)HAS-User-20120731},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P11-20150101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36883902},
      UT           = {WOS:000947818200001},
      doi          = {10.1021/acs.jmedchem.2c01887},
      url          = {https://bib-pubdb1.desy.de/record/600080},
}