Discovery of inhibitors of the metabolic oncogene 3-phosphoglycerate dehydrogenas

DESCRIPTION (provided by applicant): Many profound metabolic alterations have been described in solid tumors which present attractive therapeutic targets. One recently described metabolic oncogene is 3- phosphoglycerate dehydrogenase (PHGDH), the rate-limiting step in the pathway synthesizing serine and glycine for proteins, lipids, folate and nucleotide metabolism. The PHGDH gene is amplified at the genomic level across a wide spectrum of human cancers, and is particularly associated with certain treatment-resistant subtypes, such as triple-negative breast cancers, that present a major unmet clinical need for novel, safe and effective therapeutics. PHGDH knockdown has been demonstrated to be specifically toxic to PHGDH-amplified cell lines both in culture and in xenograft models. However, to date no specific inhibitors of mammalian PHGDH have yet been described, severely limiting investigation into this exciting new cancer target. To address this need Kadmon Corporation has initiated a project towar