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基于结构的ABCG2抑制剂发现：一种基于同源蛋白的药效团建模与分子对接方法。

Structure-Based Discovery of ABCG2 Inhibitors: A Homology Protein-Based Pharmacophore Modeling and Molecular Docking Approach.

作者信息

Le Minh-Tri, Hoang Viet-Nham, Nguyen Dac-Nhan, Bui Thi-Hoang-Linh, Phan Thien-Vy, Huynh Phuong Nguyen-Hoai, Tran Thanh-Dao, Thai Khac-Minh

机构信息

Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 100000, Vietnam.

School of Medicine, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 100000, Vietnam.

出版信息

Molecules. 2021 May 23;26(11):3115. doi: 10.3390/molecules26113115.

DOI:10.3390/molecules26113115
PMID:34071039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8197086/
Abstract

ABCG2 is an ABC membrane protein reverse transport pump, which removes toxic substances such as medicines out of cells. As a result, drug bioavailability is an unexpected change and negatively influences the ADMET (absorption, distribution, metabolism, excretion, and toxicity), leading to multi-drug resistance (MDR). Currently, in spite of promising studies, screening for ABCG2 inhibitors showed modest results. The aim of this study was to search for small molecules that could inhibit the ABCG2 pump. We first used the WISS MODEL automatic server to build up ABCG2 homology protein from 655 amino acids. Pharmacophore models, which were con-structed based on strong ABCG2 inhibitors (IC < 1 μM), consist of two hydrophobic (Hyd) groups, two hydrogen bonding acceptors (Acc2), and an aromatic or conjugated ring (Aro|PiR). Using molecular docking method, 714 substances from the DrugBank and 837 substances from the TCM with potential to inhibit the ABCG2 were obtained. These chemicals maybe favor synthesized or extracted and bioactivity testing.

摘要

ABCG2是一种ABC膜蛋白逆向转运泵，可将药物等有毒物质排出细胞。因此，药物生物利用度会出现意外变化，并对药物的吸收、分布、代谢、排泄和毒性（ADMET）产生负面影响，导致多药耐药性（MDR）。目前，尽管有一些有前景的研究，但筛选ABCG2抑制剂的结果并不理想。本研究的目的是寻找能够抑制ABCG2泵的小分子。我们首先使用WISS MODEL自动服务器从655个氨基酸构建ABCG2同源蛋白。基于强效ABCG2抑制剂（IC<1μM）构建的药效团模型由两个疏水（Hyd）基团、两个氢键受体（Acc2）和一个芳香或共轭环（Aro|PiR）组成。使用分子对接方法，从DrugBank中获得了714种物质，从中药中获得了837种具有抑制ABCG2潜力的物质。这些化学物质可能有利于合成、提取和生物活性测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e5/8197086/f86160d381ad/molecules-26-03115-g018.jpg
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