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Discovery of aldolase A inhibitors via high-throughput screening assay based on an enzymatic coupling reaction

文献类型：期刊论文

作者Xiong, Qingwen1,2; Qian, Rongyu1,2; Huang, Qingcheng2; Liu, Jingqiu2; Zhou, Chen3; Luo, Cheng1,2; Liu, Dongxiang1,2; Du, Daohai2
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2025-12-01
卷号128页码:7
关键词ALDOA Enzymatic coupling reaction High-throughput screening Inhibitor
ISSN号0960-894X
DOI10.1016/j.bmcl.2025.130332
英文摘要Aldolase A (ALDOA) is a key enzyme in glycolysis, catalyzing the reversible conversion of fructose-1,6-diphosphate (FBP) to dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). The aberrant overexpression of ALDOA is associated with the development of various solid tumors. Here, we developed an in vitro enzymatic coupling reaction assay, which demonstrates high cost-efficiency and is suitable for high-throughput screening (HTS). With this assay we identified two potential ALDOA inhibitors, merbromin and ellagic acid, from our in-house compound library. Merbromin and ellagic acid exhibit significant inhibitory activities with IC50 values of 8.49 f 0.62 mu M and 19.87 f 2.03 mu M, respectively. The nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) experiments further confirmed their high affinities to ALDOA, with the dissociation constants (Kd) of 0.49 f 0.10 mu M and 0.64 f 0.10 mu M, respectively. Enzyme kinetics experiment revealed that both compounds act as noncompetitive inhibitors of ALDOA. Our study showed that the enzymatic coupling reaction-based assay established here is highly effective and offers a promising approach for the development of ALDOA inhibitors.
WOS关键词FRUCTOSE-1,6-BISPHOSPHATE ; SUBSTRATE ; GLUCOSE
资助项目National Key Research and Development Program of China[2022YFC3400500] ; National Natural Science Foun-dation of China[92253303] ; National Natural Science Foun-dation of China[22337004] ; National Natural Science Foun-dation of China[82341017]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:001537564600001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/321117]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Liu, Dongxiang; Du, Daohai
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Jiangsu, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Xiong, Qingwen,Qian, Rongyu,Huang, Qingcheng,et al. Discovery of aldolase A inhibitors via high-throughput screening assay based on an enzymatic coupling reaction[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2025,128:7.
APA Xiong, Qingwen.,Qian, Rongyu.,Huang, Qingcheng.,Liu, Jingqiu.,Zhou, Chen.,...&Du, Daohai.(2025).Discovery of aldolase A inhibitors via high-throughput screening assay based on an enzymatic coupling reaction.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,128,7.
MLA Xiong, Qingwen,et al."Discovery of aldolase A inhibitors via high-throughput screening assay based on an enzymatic coupling reaction".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 128(2025):7.

入库方式： OAI收割

来源：上海药物研究所

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