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@ARTICLE{Poorebrahim:179694,
      author       = {M. Poorebrahim$^*$ and M. F. Abazari and L. Moradi and B.
                      Shahbazi and R. Mahmoudi and H. Kalhor and H. Askari and L.
                      Teimoori-Toolabi},
      title        = {{M}ulti-targeting of {K}-{R}as domains and mutations by
                      peptide and small molecule inhibitors.},
      journal      = {PLoS Computational Biology},
      volume       = {18},
      number       = {4},
      issn         = {1553-734X},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {DKFZ-2022-00843},
      pages        = {e1009962 -},
      year         = {2022},
      note         = {#EA:D122#},
      abstract     = {K-Ras activating mutations are significantly associated
                      with tumor progression and aggressive metastatic behavior in
                      various human cancers including pancreatic cancer. So far,
                      despite a large number of concerted efforts, targeting of
                      mutant-type K-Ras has not been successful. In this regard,
                      we aimed to target this oncogene by a combinational approach
                      consisting of small peptide and small molecule inhibitors.
                      Based on a comprehensive analysis of structural and
                      physicochemical properties of predominantly K-Ras mutants,
                      an anti-cancer peptide library and a small molecule library
                      were screened to simultaneously target oncogenic mutations
                      and functional domains of mutant-type K-Ras located in the
                      P-loop, switch I, and switch II regions. The selected
                      peptide and small molecule showed notable binding affinities
                      to their corresponding binding sites, and hindered the
                      growth of tumor cells carrying K-RasG12D and K-RasG12C
                      mutations. Of note, the expression of K-Ras downstream genes
                      (i.e., CTNNB1, CCND1) was diminished in the treated
                      Kras-positive cells. In conclusion, our combinational
                      platform signifies a new potential for blockade of oncogenic
                      K-Ras and thereby prevention of tumor progression and
                      metastasis. However, further validations are still required
                      regarding the in vitro and in vivo efficacy and safety of
                      this approach.},
      cin          = {D122},
      ddc          = {610},
      cid          = {I:(DE-He78)D122-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35472201},
      doi          = {10.1371/journal.pcbi.1009962},
      url          = {https://inrepo02.dkfz.de/record/179694},
}