Background: There has been growing interest in the development of highly potent and selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find potent and selective PTP1B inhibitors, which is currently considered as one of the best validated biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked, causing type II diabetes.

Objective: Insulin receptor sensitization is performed by a signal transduction mechanism via a selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor, autophosphorylation of the intracellular part of the receptor takes place, turning it into an active kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation. PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors.

Methods: Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives, 2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols, phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease mechanisms.

Results: The reader will gain an overview of the structure and biological activity of recently developed PTPs inhibitors.

Conclusion: The co-crystallized ligands and the screened inhibitors could be used as a template for the further design of potent congeners.

背景：在过去的2-3年中，人们对开发高效且选择性的蛋白质酪氨酸磷酸酶（PTP1B）抑制剂的兴趣日益浓厚。尽管大多数PTP具有相同的活性位点基序，但人们对选择性抑制剂（尤其是针对PTP1B的抑制剂）的兴趣正在增加，以发现新的化学实体作为降糖药。在当前寻找有效和选择性PTP1B抑制剂的范式中，目前认为PTP1B抑制剂是非胰岛素依赖型糖尿病和肥胖个体的最佳验证生物靶标之一，由于胰岛素受体敏感性降低而对胰岛素产生的耐药性是病理因素并且也有遗传联系，导致II型糖尿病。

目的：通过选择性蛋白酪氨酸磷酸酶（PTP1B）的信号转导机制进行胰岛素受体致敏。胰岛素与其受体相互作用后，受体细胞内部分发生自磷酸化，使其转变为活性激酶（敏化）。PTP1B通过脱磷酸作用参与受体的脱敏。PTP1b抑制剂可延缓受体脱敏作用，延长胰岛素作用，并使PTP1B成为治疗II型糖尿病的药物靶标。因此，它已经成为发现用于治疗II型糖尿病和肥胖症的有效药物的主要目标。在本研究中已尝试讨论蛋白质酪氨酸磷酸酶（PTP1B）抑制剂的最新设计和发现。

方法：许多PTP1B抑制剂，例如二氨基吡咯并喹唑啉，三嗪，嘧啶三嗪衍生物，2-（苄氨基）-1-苯基乙醇，尿素，乙酰胺和哌嗪基丙醇，苯基磺酰胺和苯基羧酰胺，苯甲酰氨基，芳基羧酸衍生物，芳基磺酰磺酰基衍生物，噻唑和异硫唑酮讨论了疾病机理。

结果：读者将获得最近开发的PTPs抑制剂的结构和生物学活性的概述。

结论：共结晶的配体和筛选的抑制剂可作为进一步设计有效同源物的模板。