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DM-NOFD (dimethyl N-oxalyl-D-phenylalanine) is a cell-permeable small molecule inhibitor of Factor Inhibiting HIF-1 (FIH-1), an asparaginyl hydroxylase. FIH-1 regulates the transcriptional activity of Hypoxia-Inducible Factor 1 (HIF-1) by hydroxylating the Asn803 residue in its C-terminal activation domain, a modification that blocks the recruitment of co-activators such as p300/CBP. By inhibiting FIH-1, DM-NOFD prevents this hydroxylation, thereby enhancing HIF-1-mediated gene expression even under normoxic conditions. It is widely used as a chemical tool in research to differentiate the regulatory effects of FIH-1 from those of HIF prolyl hydroxylases (PHDs).
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