Discovery of a Highly Potent and Selective MEK Inhibitor: Trametinib（MEKINIST<sup>®</sup>）

DOI
  • Abe Hiroyuki
    Chemical Research Laboratories, Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
  • Yamaguchi Takayuki
    Biological Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
  • Iida Tetsuya
    Chemical Research Laboratories, Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
  • Kikuchi Shinichi
    Chemical Research Laboratories, Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
  • Kawasaki Hisashi
    Chemical Research Laboratories, Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.

Bibliographic Information

Other Title
  • MEK阻害薬Trametinib（MEKINIST<sup>®</sup>）の創製

Abstract

<p>Trametinib is a highly potent, highly selective allosteric inhibitor of MEK1/2. However, trametinib was not discovered from pursuing MEK inhibitory activities. A lead compound was identified by a cell-based phenotypic high-throughput screening to identify those compounds that increase p15INK4b. Our synthetic efforts were directed at improving antiproliferative activity against cancer cells as well as various other drug properties. These efforts led to the discovery of highly potent and selective MEK inhibitors. Although the molecular target of trametinib was still unknown until the time that trametinib was synthesized, a chemical biological technique revealed that MEK1/MEK2 were the binding proteins of trametinib. We selected trametinib DMSO for development as the first FDA approved drug of this solvate.</p>

Journal

  • MEDCHEM NEWS

    MEDCHEM NEWS 27 (3), 129-134, 2017-08-01

    The Pharmaceutical Society of Japan

Keywords

Details 詳細情報について

  • CRID
    1390282752335484800
  • NII Article ID
    130007716549
  • DOI
    10.14894/medchem.27.3_129
  • ISSN
    24328626
    24328618
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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