Background: The discovery of novel antidiabetics for the treatment of type 2 diabetes mellitus (T2DM) is an important task nowadays because the current treatment approaches have certain limitations. The reported studies showed that the protein tyrosine phosphatase 1B (PTP1B) is a valuable target, can be used to develop significant antidiabetic molecules.

Objective: In the present investigation, computational methods and biological evaluation studies have been applied to develop novel PTP1B inhibitors with good enzyme binding affinity and activity.

Methods: Virtual screening (docking) analysis of SPECS database compounds on PTP1B enzyme was performed using Schrodinger software. In vitro and in vivo biological evaluations had been conducted with the identified hits.

Results: The results revealed that the molecules identified through these studies have shown significant interactions with the active site residues of the PTP1B enzyme. The compounds S1 and S2 provided significant binding interactions with the residues (Arg221 and Gln262) and have shown considerable in vitro PTP1B inhibitory activity and in vivo antidiabetic activity. The compounds S1 and S2 possessed 35.44±0.12% and 33.68±0.08% inhibitory activities, respectively.

Conclusion: These identified hits will be used as a template for design and development of novel PTP1B inhibitors with a compatible pharmacokinetic profile.

背景：由于目前的治疗方法存在一定的局限性，因此发现用于治疗2型糖尿病（T2DM）的新型抗糖尿病药已成为一项重要任务。报道的研究表明，蛋白质酪氨酸磷酸酶1B（PTP1B）是有价值的靶标，可用于开发重要的抗糖尿病分子。

目的：在本研究中，计算方法和生物学评估研究已用于开发具有良好酶结合亲和力和活性的新型PTP1B抑制剂。

方法：使用Schrodinger软件对SPECS数据库化合物在PTP1B酶上进行虚拟筛选（对接）分析。已经对鉴定出的命中进行了体外和体内生物学评估。

结果：结果表明，通过这些研究鉴定出的分子已显示出与PTP1B酶活性位点残基的显着相互作用。化合物S1和S2提供了与残基（Arg221和Gln262）的显着结合相互作用，并显示出显着的体外PTP1B抑制活性和体内抗糖尿病活性。化合物S1和S2分别具有35.44±0.12％和33.68±0.08％的抑制活性。

结论：这些确定的命中将被用作设计和开发具有相容药代动力学特征的新型PTP1B抑制剂的模板。