VH 298

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Cat.No. 6156 - VH 298 | C27H33N5O4S | CAS No. 2097381-85-4
Description: High-affinity inhibitor of VHL
Chemical Name: (2S,4R)-1-((S)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
Purity: ≥98% (HPLC)
Datasheet
Citations (2)
Reviews
Literature (3)

Biological Activity

High-affinity inhibitor of E3 ubiquitin ligase VHL (Kd = 80-90 nM). Blocks interaction between VHL and HIF-α downstream of HIF-α hydroxylation, initiating hypoxic response. Results in time- and concentration-dependent accumulation of hydroxylated HIF-α, and upregulates mRNA and protein levels of HIF target genes, with similar transcriptional profile to hypoxia. Cell permeable.

Negative control cis VH 298 also available.

Licensing Information

Sold under licence from the University of Dundee

External Portal Information

Chemicalprobes.org is a portal that offers independent guidance on the selection and/or application of small molecules for research. The use of VH 298 is reviewed on the Chemical Probes website.

Compound Libraries

VH 298 is also offered as part of the Tocriscreen Epigenetics Toolbox. Find out more about compound libraries available from Tocris.

Technical Data

M. Wt 523.65
Formula C27H33N5O4S
Storage Store at -20°C
Purity ≥98% (HPLC)
CAS Number 2097381-85-4
PubChem ID 122199236
InChI Key NDVQUNZCNAMROD-RZUBCFFCSA-N
Smiles O=C(N[C@@H](C(C)(C)C)C(N1C[C@@H](C[C@H]1C(NCC2=CC=C(C3=C(N=CS3)C)C=C2)=O)O)=O)C4(C#N)CC4

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 52.37 100
ethanol 52.37 100

Preparing Stock Solutions

The following data is based on the product molecular weight 523.65. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.91 mL 9.55 mL 19.1 mL
5 mM 0.38 mL 1.91 mL 3.82 mL
10 mM 0.19 mL 0.95 mL 1.91 mL
50 mM 0.04 mL 0.19 mL 0.38 mL

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References

References are publications that support the biological activity of the product.

Frost et al (2015) Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat.Commun. 7 13312 PMID: 27811928

Soares et al (2018) Group-based optimization of potent and cell-active inhibitors of the von Hippel-Lindau (VHL) E3 ubiquitin ligase: structure-activity relationships leading to the chemical probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3 J.Med.Chem. 61 599 PMID: 28853884

Frost et al (2019) RNA-seq analysis of PHD and VHL inhibitors reveals differences and similarities to the hypoxia response. Wellcome Open Res. 4 17 PMID: 30801039


If you know of a relevant reference for VH 298, please let us know.

View Related Products by Product Action

View all Ubiquitin E3 Ligase Inhibitors

Keywords: VH 298, VH 298 supplier, Inhibitors, Inhibition, VH298, VHL, HIF-alpha, HIF-a, HIF-α, cisVH298, von, Hippel-Lindau, protein, E3, ubiquitin, ligase, Hypoxia, Inducible, Factors, Ubiquitin, Ligases, 6156, Tocris Bioscience

2 Citations for VH 298

Citations are publications that use Tocris products. Selected citations for VH 298 include:

Qiu et al (2019) Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling. J Diabetes Res 2019 1897174 PMID: 30911550

Price et al (2019) Genome-Wide Interrogation of Human Cancers Identifies EGLN1 Dependency in Clear Cell Ovarian Cancers. Cancer Res 79 2564 PMID: 30898838


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Literature in this Area

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