2. Academic Validation
  3. Identification of pyruvate dehydrogenase kinase 1 inhibitors with anti-osteosarcoma activity

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.
Aiping Fang 1,  Huiqiang Luo 2,  Liping Liu 3,  Haibo Fan 3,  Yaying Zhou 3,  Yuqin Yao 1,  Yue Zhang 4
Affiliations

Affiliations

  • 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: Yue_Zhang1025@yeah.net.
PMID: 29150396 DOI: 10.1016/j.bmcl.2017.10.073
Abstract

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.

Keywords

Proliferation; Pyruvate dehydrogenase complex; Pyruvate dehydrogenase kinase; Target.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-136882
    PDHK抑制剂
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