SML1896

VH298

≥98% (HPLC)

• Synonym(s): (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
• Empirical Formula (Hill Notation): C₂₇H₃₃N₅O₄S
• CAS Number: 2097381-85-4
• Molecular Weight: 523.65
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• ligand: VH298
• Quality Level: 100
• assay: ≥98% (HPLC)
• form: powder
• reaction suitability: reagent type: ligand
• color: white to beige
• solubility: DMSO: 10 mg/mL, clear
• storage temp.: −20°C
• SMILES string: [s]1cnc(c1c2ccc(cc2)CNC(=O)[C@H]3N(C[C@@H](C3)O)C(=O)[C@@H](NC(=O)C4(CC4)C#N)C(C)(C)C)C
• InChI key: NDVQUNZCNAMROD-RZUBCFFCSA-N

Description

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.

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.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable