azd-7545 and Osteosarcoma

Pyruvate dehydrogenase kinases (PDKs) act as negative modulator of mitochondrial pyruvate dehydrogenase complex (PDC) and play a crucial role in the regulation of oxidative glycolysis, which recently have been considered as a potential drug target for varying types of cancer and diabetes. Herein, we describe the discovery and biological validation of novel anti-osteosarcoma therapeutics targeting PDK2. We identified 14 anti-osteosarcoma compounds from an in-house small molecule library, which were then evaluated in a PDK2 kinase inhibition assay. We found that compounds with 2-((4-oxo-6-((4-phenylpiperazin-1-yl)methyl)-4H-pyran-3-yl)oxy)acetamide moiety showed promising inhibitory potencies to PDK2. Especial for 12, which bound to PDK2 with a K

Topics: Acetamides; Amino Acids; Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Models, Molecular; Molecular Structure; Molecular Targeted Therapy; Osteosarcoma; Piperazines; Protein Binding; Protein Kinase Inhibitors; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Small Molecule Libraries; Structure-Activity Relationship