A Review on Branched-Chain Amino Acid Aminotransferase (BCAT) Inhibitors: Current Status, Challenges and Perspectives
文献类型：期刊论文
| 作者 | Zhang, Xiansheng1,2; Zhu, Xinyuan2,3; Li, Yong2,4; Li, Yan5; Luo, Wen2,4; Khan, Maaz2,6,7; Pan, Jiamin2,4; Pan, Hong2,8; Xie, Hua2,5; Zhao, Guilong2,3,4,6,7 |
| 刊名 | CURRENT MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025 |
| 卷号 | 32期号:42页码:9533-9554 |
| 关键词 | Branched-chain amino acid (BCAA) branched-chain amino acid aminotransferase (BCAT) BAY-069 structure-activity relationship (SAR) tumor DNA-encoded library |
| ISSN号 | 0929-8673 |
| DOI | 10.2174/0109298673320136241024054435 |
| 英文摘要 | Branched-chain amino acids (BCAAs) are essential amino acids for humans and play an indispensable role in many physiological and pathological processes. Branched-chain amino acid aminotransferase (BCAT) is a key enzyme that catalyzes the metabolism of BCAAs. BCAT is upregulated in many cancers and implicated in the development and progress of some other diseases, such as metabolic and neurological diseases; and therefore, targeting BCAT might be a potential therapeutic approach for these diseases. There are two isoforms of BCAT, i.e., cytoplasmic BCAT1 (or BCATc) and mitochondrial BCAT2 (or BCATm). The discovery of BCAT inhibitors was initiated by Warner-Lambert, a subsidiary of Pfizer, in 2000, followed by many other pharmaceutical companies, such as GlaxoSmithKline (GSK), Ergon, Icagen, Agios, and Bayer. Strategies of high-throughput screening (HTS), DNA-Encoded library technology (ELT), and fragment-based screening (FBS) have been employed for hit identification, followed by structural optimization. Despite low selectivity, both BCAT1 and BCAT2 selective inhibitors were individually developed, each with a few chemical structural classes. The most advanced BCAT1 inhibitor is BAY-069, discovered by Bayer, which has a potent enzymatic inhibitory activity against BCAT1 and a decent in vitro and in vivo pharmacokinetic profile but displayed weaker cellular inhibitory activity and almost no anti-proliferative activity. There are no BCAT inhibitors currently under investigation in clinical trials. Further studies are still needed to discover BCAT inhibitors with a more druggable profile for proof of concept. This review focuses on the latest progress of studies on the understanding of the physiology and pathology of BCAT and the discovery and development of BCAT inhibitors. The structure-activity relationship (SAR) and the druggability, and the challenges of BCAT inhibitors are discussed, with the aim of inspiring the discovery and development of BCAT inhibitors in the future. |
| WOS关键词 | PROMOTES CELL-PROLIFERATION ; CANCER PROGRESSION ; METABOLISM ; ACTIVATION ; EXPRESSION ; DISCOVERY ; GLUTAMATE ; ANTICONVULSANT ; TRANSAMINASE ; GABAPENTIN |
| 资助项目 | Guangdong Basic and Applied Basic Research Foundation[2023A1515012259] ; Zhongshan Municipal Natural Science Foundation[210730214049987] ; Zhongshan Municipal Natural Science Foundation[221018194369472] ; Creative Research Group of Zhongshan City (Lingnan Pharmaceutical Research and Innovation team)[CXTD2022011] ; Dazhou Applied Basic Research Foundation[23YYJC0002] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001603056900009 |
| 出版者 | BENTHAM SCIENCE PUBL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/320469]  |
| 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 | Xie, Hua; Zhao, Guilong |
| 作者单位 | 1.Zaozhuang Univ, Coll Food Sci & Pharmaceut Engn, Zaozhuang 277160, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 3.China Pharmaceut Univ, Sch Pharm, Nanjing 211198, Peoples R China 4.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Small Mol Drug Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.Dazhou Vocat & Tech Coll, Sch Intelligent Med Technol, Dazhou 635001, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xiansheng,Zhu, Xinyuan,Li, Yong,et al. A Review on Branched-Chain Amino Acid Aminotransferase (BCAT) Inhibitors: Current Status, Challenges and Perspectives[J]. CURRENT MEDICINAL CHEMISTRY,2025,32(42):9533-9554. |
| APA | Zhang, Xiansheng.,Zhu, Xinyuan.,Li, Yong.,Li, Yan.,Luo, Wen.,...&Zhao, Guilong.(2025).A Review on Branched-Chain Amino Acid Aminotransferase (BCAT) Inhibitors: Current Status, Challenges and Perspectives.CURRENT MEDICINAL CHEMISTRY,32(42),9533-9554. |
| MLA | Zhang, Xiansheng,et al."A Review on Branched-Chain Amino Acid Aminotransferase (BCAT) Inhibitors: Current Status, Challenges and Perspectives".CURRENT MEDICINAL CHEMISTRY 32.42(2025):9533-9554. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。