α‑Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH)

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.