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Merck

SML1896

Sigma-Aldrich

VH298

≥98% (HPLC)

Sinónimos:

(2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

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About This Item

Fórmula empírica (notación de Hill):
C27H33N5O4S
Número de CAS:
Peso molecular:
523.65
UNSPSC Code:
12352200
NACRES:
NA.77

ligand

VH298

Quality Level

assay

≥98% (HPLC)

form

powder

reaction suitability

reagent type: ligand

color

white to beige

solubility

DMSO: 10 mg/mL, clear

storage temp.

−20°C

Biochem/physiol Actions

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.

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Referencia del producto
Descripción
Precios

Storage Class

11 - Combustible Solids

wgk_germany

WGK 3

flash_point_f

Not applicable

flash_point_c

Not applicable


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Olena S Tokareva et al.
Nature communications, 14(1), 6992-6992 (2023-11-02)
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
Julianty Frost et al.
Nature communications, 7, 13312-13312 (2016-11-05)
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
Yong Hwan Kim et al.
Molecules (Basel, Switzerland), 29(2) (2024-01-23)
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
Lauren M Meyers et al.
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
Misty Shuo Zhang et al.
Nature communications, 13(1), 954-954 (2022-02-19)
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

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