10-formyltetrahydrofolate and Pancreatic-Neoplasms

Folate-dependent one-carbon (C1) metabolism is compartmentalized in the mitochondria and cytosol and is a source of critical metabolites for proliferating tumors. Mitochondrial C1 metabolism including serine hydroxymethyltransferase 2 (SHMT2) generates glycine for de novo purine nucleotide and glutathione biosynthesis and is an important source of NADPH, ATP, and formate, which affords C1 units as 10-formyl-tetrahydrofolate and 5,10-methylene-tetrahydrofolate for nucleotide biosynthesis in the cytosol. We previously discovered novel first-in-class multitargeted pyrrolo[3,2-

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Membrane; Cytosol; Drug Screening Assays, Antitumor; Gene Knockout Techniques; Glutathione; Glycine Hydroxymethyltransferase; Humans; Leucovorin; Mitochondria; Pancreatic Neoplasms; Purine Nucleotides; Pyrimidines; Pyrroles; Reactive Oxygen Species; Serine; Tetrahydrofolates