| Identification | Back Directory | [Name]
VH298 | [CAS]
2097381-85-4 | [Synonyms]
VH298
CS-2647
VH298;VH 298
VH298 USP/EP/BP
(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 | [MDL Number]
MFCD30742947 | [MOL File]
2097381-85-4.mol | [Molecular Weight]
523.65 |
| Questions And Answer | Back Directory | [Description]
VH298 is a potent VHL (Von Hippel-Lindau, the E3 ligase) inhibitor that stabilizes HIF-α. VH298 blocks the VHL:HIF-α interaction with Kd of 90 nM in isothermal titration calorimetry (ITC) and 80 nM in a competitive fluorescence polarization assay. VH-298 can be used in PROTAC technology. | [In vitro]
VH298 can activate the HIF-1 signalling pathway by stabilizing both forms of HIF-1α in vitro. VH298 promotes rFb variability, migration, and synthesis of collagen and regulatory cell factors. VH298 improves the angiogenesis of hUVEC. | [In vivo]
VH298 can activate the HIF-1 signalling pathway by stabilizing both forms of HIF-1α in vitro. VH298 promotes rFb variability, migration, and synthesis of collagen and regulatory cell factors. VH298 improves the angiogenesis of hUVEC. |
| Chemical Properties | Back Directory | [Boiling point ]
860.8±65.0 °C(Predicted) | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMF:30.0(Max Conc. mg/mL);57.29(Max Conc. mM)
DMSO:66.42(Max Conc. mg/mL);126.84(Max Conc. mM)
Ethanol:60.79(Max Conc. mg/mL);116.09(Max Conc. mM)
Ethanol:PBS (pH 7.2) (1:9):0.1(Max Conc. mg/mL);0.19(Max Conc. mM) | [form ]
A crystalline solid | [pka]
12.28±0.20(Predicted) | [color ]
Off-white to pink | [InChIKey]
NDVQUNZCNAMROD-RZUBCFFCSA-N | [SMILES]
C(NCC1=CC=C(C2SC=NC=2C)C=C1)(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@H](C(C)(C)C)NC(C1(C#N)CC1)=O |
| Hazard Information | Back Directory | [Uses]
(2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide is a VHL inhibitors that decreases hypoxia inducible factor-α during hypoxia associated signaling in human cervical cancer, osteosarcoma HeLa and U2OS. cells. | [Biological Activity]
HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signaling, and vascularization. It is is a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechan: the the blockade of the VHL: HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. It engages with high affinity and specificity with VHL as its only primary 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[1-2].
| [storage]
Store at -20°C | [References]
[1] Julianty Frost. “Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition.” Nature Communications 7 1 (2016).
[2] Shuo Qiu. “Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling.” Journal of Diabetes Research (2019): 1897174.
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