Selected article for: "active site and drug design"
Author: Schevitz, R.W.; Bach, N.J.; Carlson, D.G.; Chirgadze, N.Y.; Clawson, D.K.; Dillard, R.D.; Draheim, S.E.; Hartley, L.W.; Jones, N.D.; Mihelich, E.D.; Olkowski, J.L.; Snyder, D.W.; Sommers, C.; Wery, J.-P.
Title: Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A(2)
  • Cord-id: vzxbim9a
  • Document date: 1995_1_1
    • ID: vzxbim9a
    Snippet: A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A(2) (hnps-PLA(2)) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA(2) complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The applicat
    Document: A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A(2) (hnps-PLA(2)) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA(2) complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The application of structure-based drug design has made possible improvements in the binding of this screening lead to the enzyme by nearly three orders of magnitude. Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA(2).

    Search related documents:
    Co phrase search for related documents
    • absence presence and activate factor: 1
    • absence presence and activate factor platelet: 1
    • absence presence and active site: 1, 2, 3, 4, 5, 6, 7, 8
    • absence presence and activity enzyme: 1, 2, 3, 4
    • absence presence and activity test: 1, 2, 3
    • absence presence and acute pancreatitis: 1, 2
    • absence presence and low activity: 1, 2, 3