Ligand- and Structure-Based Drug Design Strategies and PPARδ/α Selectivity
Ligand- and Structure-Based Drug Design Strategies and PPARδ/α Selectivity
复制标题
DOI：
10.1111/j.1747-0285.2012.01424.x
复制
发表时间：
2012-10-01
影响因子：
3
通讯作者：
Honorio, Kathia M.
中科院分区：
文献类型：
--
作者：
Maltarollo, Vinicius G.;Honorio, Kathia M.
过氧化物酶体增殖物激活受体（Peroxisome-proliferator-activatedreceptor，PPR）是一类核受体，分为a、？和d.它们的主要功能是调节与脂质和碳水化合物代谢相关的基因转录。目前，还没有过氧化物酶体增殖物激活受体药物上市。在这项工作中，我们研究了70个具有a和d活性的化合物的数据集。建立了三个偏最小二乘模型，并进行了分子对接研究，以了解过氧化物酶体增殖物激活受体选择性的主要原因。所获得的结果表明，一些分子描述符（log P，水合能，空间和极性特性）相关的主要相互作用，可以直接配体的一个特定的过氧化物酶体增殖物激活受体亚型。
Peroxisome-proliferator-activated receptors are a class of nuclear receptors with three subtypes: a, ? and d. Their main function is regulating gene transcription related to lipid and carbohydrate metabolism. Currently, there are no peroxisome-proliferator-activated receptors d drugs being marketed. In this work, we studied a data set of 70 compounds with a and d activity. Three partial least square models were created, and molecular docking studies were performed to understand the main reasons for peroxisome-proliferator-activated receptors d selectivity. The obtained results showed that some molecular descriptors (log P, hydration energy, steric and polar properties) are related to the main interactions that can direct ligands to a particular peroxisome-proliferator-activated receptors subtype.