磷酸酶和激酶分别维持去磷酸化和磷酸化蛋白质的平衡，这对于维持细胞功能至关重要。当此平衡失调或它们的功能异常时，会导致不利的细胞影响，并与许多疾病的发展有关。蛋白质酪氨酸磷酸酶（PTPs）催化酪氨酸残基上的蛋白质底物去磷酸化，它们在细胞信号和疾病如癌症、炎症和代谢性疾病中的参与，使它们成为有吸引力的治疗靶点。然而，PTPs在治疗学的发展中证明是有挑战性的，并使它们赢得了无法药物治疗的不良声誉。尽管如此，在过去的十年里，对PTPs的抑制取得了巨大进展。本文介绍了小分子抑制剂对受称为丝裂原激活蛋白激酶（MAPK）磷酸酶（MKPs）亚家族的PTPs的进展。我们回顾了已被证明对MKPs的小分子抑制具有成功的策略和抑制剂发现工具，并讨论MKP抑制的未来可能会产生什么成果。

Phosphatases and kinases maintain an equilibrium of dephosphorylated and phosphorylated proteins, respectively, that are required for critical cellular functions. Imbalance in this equilibrium or irregularity in their function causes unfavorable cellular effects that have been implicated in the development of numerous diseases. Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of protein substrates on tyrosine residues, and their involvement in cell signaling and diseases such as cancer and inflammatory and metabolic diseases has made them attractive therapeutic targets. However, PTPs have proved challenging in therapeutics development, garnering them the unfavorable reputation of being undruggable. Nonetheless, great strides have been made toward the inhibition of PTPs over the past decade. Here, we discuss the advancement in small-molecule inhibition for the PTP subfamily known as the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). We review strategies and inhibitor discovery tools that have proven successful for small-molecule inhibition of the MKPs and discuss what the future of MKP inhibition potentially might yield.