丹磺酰标记鞘氨醇激酶 1 抑制剂的合成。

Synthesis of dansyl labeled sphingosine kinase 1 inhibitor.

机构信息

College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, South Korea.

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, South Korea.

出版信息

Chem Phys Lipids. 2018 Sep;215:29-33. doi: 10.1016/j.chemphyslip.2018.07.005. Epub 2018 Jul 22.

DOI:10.1016/j.chemphyslip.2018.07.005

PMID:30044952

Abstract

PF-543 is a non-sphingosine analogue with inhibitory effect against SK1, based on a Ki of 4.3 nM and 130-fold selectivity for SK1 over SK2. Since the development of PF-543, animal studies demonstrated its valuable role in multiple sclerosis, myocardial infarction, and colorectal cancer. We synthesized labeled PF-543 for biochemical studies involving SK1. Overall, the 8-step synthetic route used 3,5-dimethylphenol as the starting material. A docking study of SK1 and SK1 inhibitory activity confirmed the structural similarity between the synthetic dansyl-PF-543 and PF-543. We also provide fluorescence spectra of dansyl-PF-543.

摘要

PF-543 是一种非神经酰胺类似物，对 SK1 具有抑制作用，其 Ki 值为 4.3nM，对 SK1 的选择性是 SK2 的 130 倍。自 PF-543 开发以来，动物研究表明其在多发性硬化症、心肌梗死和结直肠癌中具有重要作用。我们合成了标记的 PF-543 用于涉及 SK1 的生化研究。总的来说，该 8 步合成路线以 3,5-二甲基苯酚为起始原料。SK1 的对接研究和 SK1 抑制活性证实了合成的丹磺酰基-PF-543 和 PF-543 之间的结构相似性。我们还提供了丹磺酰基-PF-543 的荧光光谱。