Identification of pyruvate dehydrogenase kinase 1 inhibitors with anti-osteosarcoma activity
- Bioorg Med Chem Lett. 2017 Dec 15;27(24):5450-5453. doi: 10.1016/j.bmcl.2017.10.073.
- 1. West China School of Public Health/No. 4 West China Teaching Hospital, Sichuan University, Chengdu 610041, PR China; State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
- 2. West China School of Public Health/No. 4 West China Teaching Hospital, Sichuan University, Chengdu 610041, PR China.
- 3. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University, (Shenzhen People's Hospital), Shenzhen 518020, Guangdong Province, PR China.
- 4. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University, (Shenzhen People's Hospital), Shenzhen 518020, Guangdong Province, PR China. Electronic address: [email protected].
Overexpression of pyruvate dehydrogenase kinases (PDKs), especially PDK1 has been observed in a variety of cancers. Thus, targeting PDK1 offers an attractive opportunity for the development of Cancer therapies. In this letter, we reported the identification of two novel PDK1 inhibitors as anti-osteosarcoma agents. We found that TM-1 and TM-2 inhibited PDK1 with the IC50 values of 2.97 and 3.41 μM, respectively. Furthermore, TM-1 and TM-2 dose-dependently reduced phosphorylation of pyruvate dehydrogenase complex in MG-63 osteosarcoma cells. Finally, TM-1 and TM-2 were found to inhibit the proliferation of MG-63 cells with the EC50 values of 14.5, and 11.0 μM, respectively, meaning TM-1 and TM-2 could be promising leads for the discovery of potent PDK1 inhibitors.