Adams J L, Lee D
Smithkline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Curr Opin Drug Discov Devel. 1999 Mar;2(2):96-109.
Protein serine/threonine kinases figure prominently among the molecular targets currently being pursued by the pharmaceutical industry. Given the conserved tertiary structure and catalytic mechanism of the mammalian kinase superfamily, it is not surprising that the discovery of selective inhibitors has proven to be difficult. However, in the last two years, progress has accelerated and approaches that target the ATP binding site and antisense RNA have matured to the point of advancing compounds into clinical trials. The development of a structural basis for understanding the selectivity of the pyridinylimidazole class of p38 MAP kinase inhibitors has been a major advance in this area.
蛋白质丝氨酸/苏氨酸激酶是制药行业目前正在研究的主要分子靶点之一。鉴于哺乳动物激酶超家族保守的三级结构和催化机制，选择性抑制剂的发现一直颇具难度也就不足为奇了。然而，在过去两年中，研究进展加速，针对ATP结合位点和反义RNA的方法已成熟到可将化合物推进临床试验阶段。构建理解p38丝裂原活化蛋白激酶（MAP激酶）抑制剂吡啶基咪唑类选择性的结构基础，是该领域的一项重大进展。
