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Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase*
The compound U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibitExpand
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Enzymes: A Practical Introduction to Structure, Mechanism, and Data Analysis
A Brief History of Enzymology. Chemical Bonds and Reactions in Biochemistry. Structural Components of Enzymes. Protein-Ligand Binding Equilibria. Kinetics of Single-Substrate Enzyme Reactions.Expand
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Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists.
  • R. Copeland
  • Chemistry, Medicine
  • Methods of biochemical analysis
  • 28 March 2005
Foreword. Preface. Acknowledgments. 1. Why Enzymes as Drug Targets? 1.1 Enzymes Are Essentials for Life. 1.2 Enzyme Structure and Catalysis. 1.3 Permutations of Enzyme Structure During Catalysis. 1.4Expand
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MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.
In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificityExpand
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Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor.
Mislocated enzymatic activity of DOT1L has been proposed as a driver of leukemogenesis in mixed lineage leukemia (MLL). The characterization of EPZ004777, a potent, selective inhibitor of DOT1L isExpand
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Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas
EZH2, the catalytic subunit of the PRC2 complex, catalyzes the mono- through trimethylation of lysine 27 on histone H3 (H3K27). Histone H3K27 trimethylation is a mechanism for suppressingExpand
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A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells.
EZH2 catalyzes trimethylation of histone H3 lysine 27 (H3K27). Point mutations of EZH2 at Tyr641 and Ala677 occur in subpopulations of non-Hodgkin's lymphoma, where they drive H3K27Expand
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Potent inhibition of DOT1L as treatment of MLL-fusion leukemia.
Rearrangements of the MLL gene define a genetically distinct subset of acute leukemias with poor prognosis. Current treatment options are of limited effectiveness; thus, there is a pressing need forExpand
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Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2
Inactivation of the switch/sucrose nonfermentable complex component SMARCB1 is extremely prevalent in pediatric malignant rhabdoid tumors (MRTs) or atypical teratoid rhabdoid tumors. This alterationExpand
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Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.
Akt kinases 1, 2, and 3 are important regulators of cell survival and have been shown to be constitutively active in a variety of human tumors. GSK690693 is a novel ATP-competitive, low-nanomolarExpand
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