近日，美国研究人员研发出一种能用于治疗糖尿病的新型化合物，与现有药物相比，它能改善血糖水平，却没有相关副作用。

美国斯克里普斯研究所等机构的研究人员报告说，这种新型化合物名为SR1664，作用原理是通过干扰某些蛋白质的功能来帮助治疗糖尿病。

研究人员用SR1664和现有降糖药物文迪雅分别治疗患有糖尿病的实验鼠，结果显示两者都能改善实验鼠的血糖水平，但文迪雅有使实验鼠体重增加等副作用，新的化合物则没有相关副作用。

此外，实验室细胞培养研究还显示，该化合物也不存在文迪雅等降糖药物影响骨骼的副作用。

文迪雅曾是流行的糖尿病药物，但近来发现其副作用明显，美国等一些国家已下令将其全面下架。因此，寻找新的无副作用的糖尿病药物成了研究热点。

领导该项研究的帕特里克·格里芬说，SR1664的作用目标是那些已知的糖尿病治疗靶点，但其发挥作用的机制独特，因此既有治疗功能又没有某些副作用。研究人员将努力在其基础上开发出用于临床治疗的药物。

原文摘要：

Antidiabetic actions of a non-agonist PPAR[ggr] ligand blocking Cdk5-mediated phosphorylation

Jang Hyun Choi; Alexander S. Banks; Theodore M. Kamenecka; Scott A. Busby; Michael J. Chalmers; Naresh Kumar; Dana S. Kuruvilla; Youseung Shin; Yuanjun He; John B. Bruning; David P. Marciano; Michael D. Cameron; Dina Laznik; Michael J. Jurczak; Stephan C. Schürer; Du?ica Vidovi?; Gerald I. Shulman; Bruce M. Spiegelman; Patrick R. Griffin

PPARγ is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone1. These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPARγ-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARγ by Cdk5 (ref. 2). Here we describe novel synthetic compounds that have a unique mode of binding to PPARγ, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPARγ drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARγ.