For research use only. Not for therapeutic Use.
VH-298(CAT: I012023) is 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. VH298 represents a high-quality chemical probe of the HIF signaling cascade and an attractive starting point for developing potential new therapeutics targeting hypoxia signaling.
Catalog Number | I012023 |
CAS Number | 2097381-85-4 |
Synonyms | VH-298; VH 298; VH298.;(2S,4R)-1-((S)-2-(1-cyanocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide |
Molecular Formula | C27H33N5O4S |
Purity | ≥95% |
Target | Ligands for E3 Ligase |
Solubility | Soluble in DMSO |
Storage | Store at 0-8 °C |
InChI | InChI=1S/C27H33N5O4S/c1-16-21(37-15-30-16)18-7-5-17(6-8-18)12-29-23(34)20-11-19(33)13-32(20)24(35)22(26(2,3)4)31-25(36)27(14-28)9-10-27/h5-8,15,19-20,22,33H,9-13H2,1-4H3,(H,29,34)(H,31,36)/t19-,20+,22-/m1/s1 |
InChIKey | NDVQUNZCNAMROD-RZUBCFFCSA-N |
SMILES | O=C([C@H]1N(C([C@@H](NC(C2(CC2)C#N)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC3=CC=C(C4=C(C)N=CS4)C=C3 |
Reference | </br>1: Soares P, Gadd MS, Frost J, Galdeano C, Ellis LCJ, Epemolu O, Rocha S, Read</br> KD, Ciulli A. Group-based optimization of potent and cell-active inhibitors of</br> the von Hippel-Lindau (VHL) E3 ubiquitin ligase: structure-activity relationships</br> leading to the chemical probe</br> (2S,4R)-1-((S)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy</br> -N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298). J Med Chem.</br> 2017 Aug 30. doi: 10.1021/acs.jmedchem.7b00675. [Epub ahead of print] PubMed</br> PMID: 28853884.</br>2: Frost J, Galdeano C, Soares P, Gadd MS, Grzes KM, Ellis L, Epemolu O,</br> Shimamura S, Bantscheff M, Grandi P, Read KD, Cantrell DA, Rocha S, Ciulli A.</br> Potent and selective chemical probe of hypoxic signalling downstream of HIF-α</br> hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312. doi:</br> 10.1038/ncomms13312. PubMed PMID: 27811928; PubMed Central PMCID: PMC5097156.</br></br> |