Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
Bioorg Med Chem Lett. 2012 Feb 1;22(3):1402-7. doi: 10.1016/j.bmcl.2011.12.042. Epub 2011 Dec 21.
In this study, we analyzed the structure-activity relationship properties of the small molecule Jak2 inhibitor G6. We synthesized a set of derivatives containing the native para-hydroxyl structure or an alternative meta-hydroxyl structure and examined their Jak2 inhibitory properties. We found that the para-hydroxyl derivative known as NB15 had excellent Jak2 inhibitory properties in silico, in vitro, and ex vivo when compared with meta-hydroxyl derivatives. These results indicate that NB15 is a potent derivative of the Jak2 inhibitor G6, and that maintaining the para-hydroxyl orientation of G6 is critical for its Jak2 inhibitory potential.
在这项研究中，我们分析了小分子 Jak2 抑制剂 G6 的结构-活性关系特性。我们合成了一组包含天然对羟基结构或替代间羟基结构的衍生物，并研究了它们对 Jak2 的抑制特性。我们发现，与间羟基衍生物相比，具有已知对羟基衍生物的 NB15 在计算机模拟、体外和体内都具有优异的 Jak2 抑制特性。这些结果表明，NB15 是 Jak2 抑制剂 G6 的有效衍生物，并且保持 G6 的对羟基取向对于其 Jak2 抑制潜力至关重要。
