Synonyms: (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
Molecular Formula: C27H33N5O4S
Molecular Weight: 523.65
Linear Structural Formula: C27H33N5O4S
Purity: >=98% (HPLC)
Storage: -20C
Biochem Physiol Actions: VH298 is a cell-permeable small molecule that disrupts the interaction of VHL with Hypoxia-inducible factor HIF-alpha, stabilizing HIF-alpha and inducing a hypoxic response. Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors that regulate hypoxic signalling. They are regulated by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes and polyubiquitination by the von Hippel-Lindau (VHL) Cullin RING E3 ubiquitin ligase complex. Unlike many PHD inhibitors, which have off-target effects, VH298 acts downstream of the PHD enzymes, inhibiting the VHL:HIF-alpha interaction. VH298 had a Kd of 90 nM. VH298 was shown to induce HIF transcriptional activity, to increase accumulation of HIF-alpha in HeLa cells and to stimulate erythropoietin production in RCC4 cells.