Computer-aided discovery and biological characterization of human lactate dehydrogenase 5 inhibitors with anti-osteosarcoma activity |
| |
| Authors: | Wei Cao Le Fang Siyong Teng Hongwei Chen Zhan Wang |
| |
| Affiliation: | 1. Clinical Laboratory of Beijing Rehabilitation Hospital of Capital Medical University, Xixia Zhuang, Bada Chu, Shijingshan District, Beijing, China;2. Department of Blood Transfusion, 521 Hospital of Ordnance Industry, Xi’an, China;3. National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, China;4. Shanghai Songjiang District Central Hospital, Yuanzhong Road, Songjiang District, Shanghai, China;5. Department of Orthopaedics, Gansu Provincial Hospital, Lanzhou, Gansu, China |
| |
| Abstract: | Human lactate dehydrogenase 5 (hLDH5) is overexpressed in various tissues of human tumors, which could be a potential therapeutic target for cancer treatment. Herein, we describe the computer-aided discovery and biological characterizations of hLDH5 inhibitors with anti-osteosarcoma activity. Biochemical assay indicated that the identified compounds 3 and 9 strongly inhibited hLDH5 function with EC50 values of 0.67 and 0.39?µM, respectively. The MTT assay revealed that most of the identified inhibitors had little effect on MG-63 cell proliferation at 4?µM, only 9 reduced the cancer cell proliferation at the same concentration, with an IC50 value of 3.18?µM. Our data suggested that 9 could be a starting lead of developing potent hLDH5 inhibitor for the anti-osteosarcoma agents in cancer treatment. |
| |
| Keywords: | Cancer metabolism Anticancer drug Metabolic reprogramming Virtual screening Proliferation |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
