Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, and several PTPs have been validated as therapeutic targets for human diseases. Historically, the development of drugs targeting PTPs has been highly challenging, leading to stigmatization of these enzymes as undruggable targets. Despite these difficulties, efforts to drug PTPs have persisted, and recent years have seen an influx of new probes providing opportunities for biological examination of old and new PTP targets. Here we discuss progress towards drugging PTPs with special emphasis on the development of selective probes with biological activity. We describe the development of new small-molecule orthosteric, allosteric, and oligomerization-inhibiting PTP inhibitors and discuss new studies targeting the receptor PTP (RPTP) subfamily with biologics.

蛋白质酪氨酸磷酸酶（PTP）是许多细胞过程必不可少的酶家族，几种PTP已被证实可作为人类疾病的治疗靶标。从历史上看，针对PTP的药物的开发一直具有很高的挑战性，导致这些酶被污名化为不可消耗的靶标。尽管有这些困难，对PTP进行药物治疗的努力仍在继续，并且近年来涌现了新的探针，这些探针为新旧PTP靶标的生物学检查提供了机会。在这里，我们讨论了对PTP给药的进展，特别着重于具有生物活性的选择性探针的开发。我们描述了新的小分子正构，变构，