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VH298 is a cell permeable high-affinity inhibitor of E3 ubiquitin ligase VHL (Kd = 80-90 nM). It blocks interaction between VHL and HIF-α downstream of HIF-α hydroxylation, initiating a hypoxic response. Results in time- and concentration-dependent accumulation of hydroxylated HIF-α, and upregulates mRNA and protein levels of HIF target genes.
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