SHMT2 and neoplasm: In conclusion,our results document novel first-in-class conformationallyflexible pyrrolo[3,2-d]pyrimidine antifolate inhibitorswhich provide tumor selectivity via FR selectivity and inhibitionof multiple essential metabolic pathways for malignant cells includingmitochondrial C1 metabolism at SHMT2 and de novo purinenucleotide biosynthesis at GARFTase and ATIC.