VH298 is a cell-permeable small molecule that disrupts the interaction of VHL with Hypoxia-inducible factor HIF-α, stabilizing HIF-α and inducing a hypoxic response.
VH298 is a cell-permeable small molecule that disrupts the interaction of VHL with Hypoxia-inducible factor HIF-α, stabilizing HIF-α 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-α interaction. VH298 had a Kd of 90 nM. VH298 was shown to induce HIF transcriptional activity, to increase accumulation of HIF-α in HeLa cells and to stimulate erythropoietin production in RCC4 cells.
Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here
Molecules that induce novel interactions between proteins hold great promise for the study of biological systems and the development of therapeutics, but their discovery has been limited by the complexities of rationally designing interactions between three components, and because known
Autophagy is a pivotal biological process responsible for maintaining the homeostasis of intracellular organelles. Yet the molecular intricacies of peroxisomal autophagy (pexophagy) remain largely elusive. From a ubiquitin-related chemical library for screening, we identified several inhibitors of the Von Hippel-Lindau
Toxicology and applied pharmacology, 445, 116041-116041 (2022-05-04)
Transcription factors HIF1 and HIF2 are central regulators of physiological responses to hypoxia and important for normal functioning of tissue stem cells and maintenance of healthy microvasculature. Even modest decreases in HIF activity exert detrimental effects in tissues although it
Hepatocellular carcinoma (HCC) invariably exhibits inadequate O2 (hypoxia) and nutrient supply. Hypoxia-inducible factor (HIF) mediates cascades of molecular events that enable cancer cells to adapt and propagate. Macropinocytosis is an endocytic process initiated by membrane ruffling, causing the engulfment of
Questions
Reviews
★★★★★ No rating value
Active Filters
Notre équipe de scientifiques dispose d'une expérience dans tous les secteurs de la recherche, notamment en sciences de la vie, science des matériaux, synthèse chimique, chromatographie, analyse et dans de nombreux autres domaines..
