VH-298

SKU: orb1296188

Description

VH-298 is a cell-permeable small molecule that potently inhibits the VHL-HIF-α interaction, stabilizing HIF-α and inducing a hypoxic response independent of PHD enzyme inhibition. It is a valuable chemical probe for studying hypoxia signaling pathways and has demonstrated utility in both cellular assays and in vivo models for angiogenesis and ischemia research.

Research Area

Cardiovascular Research, Epigenetics & Chromatin, Metabolism Research, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 2097381-85-4
• MW: 523.65
• Purity: >99.99% (May vary between batches)
• Formula: C₂₇H₃₃N₅O₄S
• SMILES: Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(CC2)C#N)C(C)(C)C)cc1
• Target: HIF,HIF/HIF Prolyl-Hydroxylase,Ligands for E3 Ligase
• Solubility: DMSO:78.3 mg/mL (149.53 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.82 mM)

Bioactivity

• Target IC50:
  VHL/HIFα:80 to 90 nM (Kd)
• In Vitro:
  VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

VH298, VH-298, VH 298, VHL, E3 ligase-recruiting Moiety, HIF-1α, Inhibitor, inhibit, Ligands for E3 Ligase, LigandforE3Ligase, Ligand for E3 Ligase

Compound Identifiers

PubChem CID

122199236