title: α-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH).
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.
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , 73 avenue Mounier, B-1200 Brussels, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ravez
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain , B-1200 Brussels, Belgium.
authors.forename: Cyril
authors.initials: C
authors.lastname: Corbet
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , 73 avenue Mounier, B-1200 Brussels, Belgium.|Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain , B-1200 Brussels, Belgium.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Spillier
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , 73 avenue Mounier, B-1200 Brussels, Belgium.
authors.forename: Alice
authors.initials: A
authors.lastname: Dutu
authors.affiliation: Meyer Cancer Center and Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Anita D
authors.initials: AD
authors.lastname: Robin
authors.affiliation: Meyer Cancer Center and Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Edouard
authors.initials: E
authors.lastname: Mullarky
authors.affiliation: Meyer Cancer Center and Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain , B-1200 Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , 73 avenue Mounier, B-1200 Brussels, Belgium.
authors.forename: Raphaël
authors.identifier: 0000-0001-8119-1272
authors.initials: R
authors.lastname: Frédérick
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D050543:Phosphoglycerate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013854:Thioamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013854:Thioamides; D050543:Phosphoglycerate Dehydrogenase