Abstract
Given the putative role of PHGDH in cancer, development of inhibitors is required to explore its function. In this context, we established and validated a straightforward enzymatic assay suitable for high-throughput screening and we identified inhibitors with similar chemical scaffolds. Through a convergent pharmacophore approach, we synthesized α-ketothioamides that exhibit interesting in vitro PHGDH inhibition and encouraging cellular results. These novel probes may be used to understand the emerging biology of this metabolic target.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Drug Evaluation, Preclinical
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology*
-
High-Throughput Screening Assays
-
Humans
-
Neoplasms / drug therapy
-
Neoplasms / enzymology
-
Phosphoglycerate Dehydrogenase / antagonists & inhibitors*
-
Phosphoglycerate Dehydrogenase / metabolism
-
Thioamides / chemistry*
-
Thioamides / pharmacology*
Substances
-
Antineoplastic Agents
-
Enzyme Inhibitors
-
Thioamides
-
Phosphoglycerate Dehydrogenase