Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms
文献类型：期刊论文
| 作者 | Xu, Yuan1; Liu, Xian1; Wang, Yulan1; Zhou, Nannan1; Peng, Jianlong1; Gong, Likun2 ; Ren, Jing2; Luo, Cheng1; Luo, Xiaomin1; Jiang, Hualiang1,3
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2015-09-02 |
| 卷号 | 5 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep13684 |
| 文献子类 | Article |
| 英文摘要 | A combinatorial pharmacophore (CP) model for Multidrug and toxin extrusion 1 (MATE1/SLC47A1) inhibitors was developed based on a data set including 881 compounds. The CP model comprises four individual pharmacophore hypotheses, HHR1, DRR, HHR2 and AAAP, which can successfully identify the MATE1 inhibitors with an overall accuracy around 75%. The model emphasizes the importance of aromatic ring and hydrophobicity as two important structural determinants for MATE1 inhibition. Compared with the pharmacophore model of Organic Cation Transporter 2 (OCT2/SLC22A2), a functional related transporter of MATE1, the hypotheses of AAAP and PRR5 are suggested to be responsible for their ligand selectivity, while HHR a common recognition pattern for their dual inhibition. A series of analysis including molecular sizes of inhibitors matching different hypotheses, matching of representative MATE1 inhibitors and molecular docking indicated that the small inhibitors matching HHR1 and DRR involve in competitive inhibition, while the relatively large inhibitors matching AAAP are responsible for the noncompetitive inhibition by locking the conformation changing of MATE1. In light of the results, a hypothetical model for inhibiting transporting mediated by MATE1 was proposed. |
| WOS关键词 | ORGANIC CATION TRANSPORTER-2 ; MATE1 ; DATABASE ; PROTEIN ; KIDNEY |
| 资助项目 | National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[81430084] ; National Natural Science Foundation of China[2014AA01A302] ; HiTech Research and Development Program of China[2012AA020308] ; Ministry of Science and Technology of China[2015CB910304] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507002-005-012] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09301001-006] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000360540600001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276403]  |
| 专题 | 药物安全性评价中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Gong, Likun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yuan,Liu, Xian,Wang, Yulan,et al. Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms[J]. SCIENTIFIC REPORTS,2015,5. |
| APA | Xu, Yuan.,Liu, Xian.,Wang, Yulan.,Zhou, Nannan.,Peng, Jianlong.,...&Zheng, Mingyue.(2015).Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms.SCIENTIFIC REPORTS,5. |
| MLA | Xu, Yuan,et al."Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms".SCIENTIFIC REPORTS 5(2015). |
入库方式： OAI收割
来源：上海药物研究所
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