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@ARTICLE{DeVita:141252,
      author       = {E. De Vita$^*$ and P. Schüler$^*$ and S. Lovell and J.
                      Lohbeck$^*$ and S. Kullmann$^*$ and E. Rabinovich and A.
                      Sananes and B. Heßling$^*$ and V. Hamon and N. Papo and J.
                      Hess$^*$ and E. W. Tate and N. Gunkel$^*$ and A. Miller$^*$},
      title        = {{D}epsipeptides {F}eaturing a {N}eutral {P}1 {A}re {P}otent
                      {I}nhibitors of {K}allikrein-{R}elated {P}eptidase 6 with
                      {O}n-{T}arget {C}ellular {A}ctivity.},
      journal      = {Journal of medicinal chemistry},
      volume       = {61},
      number       = {19},
      issn         = {1520-4804},
      address      = {Washington, DC},
      publisher    = {ACS},
      reportid     = {DKFZ-2018-01772},
      pages        = {8859 - 8874},
      year         = {2018},
      abstract     = {Kallikrein-related peptidase 6 (KLK6) is a secreted serine
                      protease that belongs to the family of tissue kallikreins
                      (KLKs). Many KLKs are investigated as potential biomarkers
                      for cancer as well as therapeutic drug targets for a number
                      of pathologies. KLK6, in particular, has been implicated in
                      neurodegenerative diseases and cancer, but target validation
                      has been hampered by a lack of selective inhibitors. This
                      work introduces a class of depsipeptidic KLK6 inhibitors,
                      discovered via high-throughput screening, which were found
                      to function as substrate mimics that transiently acylate the
                      catalytic serine of KLK6. Detailed structure-activity
                      relationship studies, aided by in silico modeling, uncovered
                      strict structural requirements for potency, stability, and
                      acyl-enzyme complex half-life. An optimized scaffold,
                      DKFZ-251, demonstrated good selectivity for KLK6 compared to
                      other KLKs, and on-target activity in a cellular assay.
                      Moreover, DKFZ-633, an inhibitor-derived activity-based
                      probe, could be used to pull down active endogenous KLK6.},
      cin          = {G404 / G405 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)G404-20160331 / I:(DE-He78)G405-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30212625},
      doi          = {10.1021/acs.jmedchem.8b01106},
      url          = {https://inrepo02.dkfz.de/record/141252},
}