Lyon Michael A, Ducruet Alexander P, Wipf Peter, Lazo John S
Department of Chemistry, Chevron Science Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Nat Rev Drug Discov. 2002 Dec;1(12):961-76. doi: 10.1038/nrd963.
Dual-specificity protein phosphatases are a subclass of protein tyrosine phosphatases that are uniquely able to hydrolyse the phosphate ester bond on both a tyrosine and a threonine or serine residue on the same protein. Dual-specificity phosphatases have a central role in the complex regulation of signalling pathways that are involved in cell stress responses, proliferation and death. Although this enzyme family is increasingly the target of drug discovery efforts in pharmaceutical companies, a summary of the salient developments in the biology and medicinal chemistry of dual-specificity phosphatases has been lacking. We hope that this comprehensive overview will stimulate further progress in the development of small-molecule inhibitors that could form the basis for a new class of target-directed therapeutic agents.
双特异性蛋白磷酸酶是蛋白酪氨酸磷酸酶的一个亚类，其独特之处在于能够水解同一蛋白质上酪氨酸以及苏氨酸或丝氨酸残基上的磷酸酯键。双特异性磷酸酶在参与细胞应激反应、增殖和死亡的信号通路的复杂调控中发挥着核心作用。尽管该酶家族日益成为制药公司药物研发工作的靶点，但一直缺乏对双特异性磷酸酶生物学和药物化学显著进展的总结。我们希望这一全面综述将推动小分子抑制剂研发取得进一步进展，这些抑制剂可能成为一类新型靶向治疗药物的基础。
