Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
Bioorg Med Chem Lett. 2012 Oct 15;22(20):6333-7. doi: 10.1016/j.bmcl.2012.08.081. Epub 2012 Aug 29.
Receptor protein tyrosine phosphatase sigma (PTPσ) has proved to be a promising target for the development of therapeutics for the treatment of neurological diseases. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule inhibitors of PTPσ. These inhibitors revealed high potencies with the associated IC(50) values ranging from 0.1 to 1.3 μM and were also screened for having desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure-activity relationship studies to develop therapeutics for neurological diseases. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTPσ are discussed in detail.
受体蛋白酪氨酸磷酸酯酶 sigma（PTPσ）已被证明是开发治疗神经疾病疗法的有前途的靶标。在这里，我们报告了首例成功应用基于结构的虚拟筛选来鉴定 PTPσ 的新型小分子抑制剂的实例。这些抑制剂显示出高活性，相关的 IC50值范围为 0.1 至 1.3 μM，并且还被筛选出具有作为候选药物的理想物理化学性质。因此，它们值得进一步通过构效关系研究来开发用于治疗神经疾病的治疗药物。详细讨论了与新鉴定的抑制剂在 PTPσ活性部位稳定相关的结构特征。
