title: Challenges and Opportunities in the Development of Serine Synthetic Pathway Inhibitors for Cancer Therapy.
abstract: Recent advances in the understanding of the relationship between cancer and metabolism have highlighted the relevance of the serine synthetic pathway (SSP), which consists of three successive enzymatic reactions. Enzymes of the SSP, such as phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT-1), were recently highlighted because they are amplified in a significant subset of human tumors, and their suppression by RNAi caused a decrease in cancer cell survival and growth. Currently, the discovery of drugs that inhibit these enzymes is still in its infancy, and the identification of suitable inhibitors could serve to understand the emerging biology of these metabolic enzymes. In this review, we present the SSP as a significant and novel emerging area for medicinal chemistry and we provide an overview of one of the key enzymes of the pathway, PHGDH.
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , Brussels 1200, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ravez
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain , Brussels 1200, Belgium.|Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain , Brussels 1200, 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 , Brussels 1200, Belgium.
authors.forename: Romain
authors.initials: R
authors.lastname: Marteau
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain , Brussels 1200, 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 , Brussels 1200, Belgium.
authors.forename: Raphaël
authors.identifier: 0000-0001-8119-1272
authors.initials: R
authors.lastname: Frédérick
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D053898:Biosynthetic Pathways / Q000187:drug effects*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D050543:Phosphoglycerate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D012694:Serine; D050543:Phosphoglycerate Dehydrogenase; D000637:Transaminases; C022393:phosphoserine aminotransferase; D005947:Glucose