VH298
- CAS No.
- 2097381-85-4
- Chemical Name:
- VH298
- Synonyms
- VH298;VHL-298;CS-2647;VH298;VH 298;VH298 USP/EP/BP;E3 ligase-recruiting Moiety,VH-298,Inhibitor,VH298,Ligands for E3 Ligase,VH 298,inhibit;L-Prolinamide, N-[(1-cyanocyclopropyl)carbonyl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-, (4R)-;(2S,4R)-1-((S)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-2-(1-Cyanocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
- CBNumber:
- CB73344894
- Molecular Formula:
- C27H33N5O4S
- Molecular Weight:
- 523.65
- MDL Number:
- MFCD30742947
- MOL File:
- 2097381-85-4.mol
| Boiling point | 860.8±65.0 °C(Predicted) |
|---|---|
| Density | 1.33±0.1 g/cm3(Predicted) |
| storage temp. | 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 |
VH298 price More Price(19)
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Cayman Chemical | 21133 | VH298 ≥98% | 2097381-85-4 | 1mg | $37 | 2024-03-01 | Buy |
| Cayman Chemical | 21133 | VH298 ≥98% | 2097381-85-4 | 5mg | $98 | 2024-03-01 | Buy |
| Cayman Chemical | 21133 | VH298 ≥98% | 2097381-85-4 | 10mg | $178 | 2024-03-01 | Buy |
| Cayman Chemical | 21133 | VH298 ≥98% | 2097381-85-4 | 25mg | $397 | 2024-03-01 | Buy |
| Tocris | 6156 | VH298 ≥98%(HPLC) | 2097381-85-4 | 10 | $244 | 2021-12-16 | Buy |
VH298 Chemical Properties,Uses,Production
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.
Description
VH-298 is a E3 ligase ligand-linker conjugate that couples the VHL ligand and blocks the interaction between VHL and HIF-α, initiating hypoxic response.
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.
VH298 Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Hubei Chuchang Biotech Co., Ltd. | +undefined15623860702 | info@chuchangbiotech.com | China | 116 | 58 |
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32951 | 60 |
| career henan chemical co | +86-0371-86658258 +8613203830695 | sales@coreychem.com | China | 29885 | 58 |
| BOC Sciences | +1-631-485-4226 | inquiry@bocsci.com | United States | 19553 | 58 |
| Chongqing Chemdad Co., Ltd | +86-023-6139-8061 +86-86-13650506873 | sales@chemdad.com | China | 39894 | 58 |
| Dideu Industries Group Limited | +86-29-89586680 +86-15129568250 | 1026@dideu.com | China | 23025 | 58 |
| Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | sales@sarms4muscle.com | China | 10473 | 58 |
| CR Corporation Limited | +8613062833949 | fred.wen@crcorporation.cn | China | 8647 | 58 |
| Labnetwork lnc. | +86-27-50766799 +8618062016861 | contact@labnetwork.com | China | 19987 | 58 |
| InvivoChem | +1-708-310-1919 +1-13798911105 | sales@invivochem.cn | United States | 6391 | 58 |
