Lee Joo-Youn, Cho Hyunkyung, Thangapandian Sundarapandian, Lim Chaemin, Chun Young-Jin, Lee Yoonji, Choi Sun, Kim Sanghee
College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Chemical Data-Driven Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea.
ACS Med Chem Lett. 2018 Oct 29;9(12):1247-1252. doi: 10.1021/acsmedchemlett.8b00409. eCollection 2018 Dec 13.
Although several families of compounds have been identified as scaffolds for inhibitors of the CYP1 family, the isoform selectivity determining structural features has not been fully clarified at the molecular interaction level. We studied the CYP1 isoform selectivity for stilbenoid inhibitors using integrated induced fit docking and molecular dynamics simulations. The hydrophobic interactions with the specific phenylalanine residues in the F helix are correlated with inhibitory potency in the CYP1 family. Through this study, we found that the adaptable, small, and semirigid ligand is a promising starting point for the development of isoform-selective inhibitors and investigation of selectivity-determining features.
尽管已鉴定出几类化合物作为CYP1家族抑制剂的骨架，但在分子相互作用水平上，决定同工型选择性的结构特征尚未完全阐明。我们使用整合诱导契合对接和分子动力学模拟研究了芪类抑制剂对CYP1同工型的选择性。与F螺旋中特定苯丙氨酸残基的疏水相互作用与CYP1家族中的抑制效力相关。通过这项研究，我们发现适应性强、体积小且半刚性的配体是开发同工型选择性抑制剂和研究选择性决定特征的有前景的起点。
