| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 500mg |
| Targets |
VHL: von Hippel-Lindau protein
VH032 targets the von Hippel-Lindau (VHL) E3 ubiquitin ligase. By binding to VHL, it disrupts the VHL:HIF-1α interaction. This prevents the ubiquitination and subsequent degradation of HIF-1α, leading to the stabilization of HIF-1α. In the context of PROTACs, VH032 serves as the VHL-recruiting ligand. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
In vitro, VH032 is a potent inhibitor of the VHL interaction with HIF-1α. It demonstrates a VHL/HIF-1α interaction inhibition Kd of 185 nM. It suppresses glioma proliferation by inhibiting the VHL/HIF-1α/VEGF pathway. |
| ln Vivo |
In vivo, VH032 has been shown to suppress glioma proliferation in xenograft mouse models. Its inhibitory effect on the VHL/HIF-1α/VEGF signaling pathway has been confirmed, supporting its role in reducing tumor growth.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for VH032 involve measuring its binding affinity to the VHL protein. This is typically done using surface plasmon resonance (SPR) or fluorescence polarization (FP) assays. The Kd for the VHL:HIF-1α interaction inhibition is determined.
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| Cell Assay |
In vitro cell-based experiments for VH032 are conducted using cancer cell lines, such as glioma cells. Cells are treated with VH032, and the expression of HIF-1α, VEGF, and other downstream targets is assessed by Western blot. Cell proliferation, migration, and invasion are measured.
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| Animal Protocol |
In vivo animal experiments for VH032 are performed in xenograft mouse models of glioma. VH032 is administered, and tumor growth, angiogenesis, and the VHL/HIF-1α/VEGF pathway are assessed.
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| ADME/Pharmacokinetics |
VH032 is a small molecule with favorable properties for research use. Its pharmacokinetic profile is suitable for in vivo studies.
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| Toxicity/Toxicokinetics |
VH032 is well-tolerated in preclinical studies. No significant toxicity has been reported.
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| References |
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| Additional Infomation |
The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 are key regulators of transcription, epigenetics, and cancer, and serve as the targets of the pan-BET selective bromodomain inhibitor JQ1. However, the lack of selectivity among BET family members limits the utility of current inhibitors for target validation and may lead to off-target effects or toxicity in therapeutic applications. To address this, we designed Proteolysis-Targeting Chimeras (PROTACs) that link JQ1 to a ligand for the E3 ubiquitin ligase VHL, aiming to induce targeted degradation of BET proteins. One such compound, MZ1, potently and rapidly induces reversible, long-lasting, and unexpectedly selective degradation of BRD4 over BRD2 and BRD3. This activity is dependent on VHL binding and occurs at concentrations low enough to avoid stabilization of HIF-1α. Analysis of gene expression profiles of cancer-related genes responsive to JQ1 reveals that MZ1 induces a distinct and more restricted transcriptional response, consistent with selective suppression of BRD4. These findings open new avenues for exploring the cellular functions and therapeutic potential of selective BRD4 targeting. [1]
VH032 is also known as VH-032 and VH 032. It is a research compound used as a VHL ligand and a tool for studying the hypoxia pathway and PROTAC development. It is not approved for clinical use. |
| Molecular Formula |
C24H32N4O4S
|
|---|---|
| Molecular Weight |
472.600284576416
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| Exact Mass |
472.214
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| Elemental Analysis |
C, 60.99; H, 6.83; N, 11.86; O, 13.54; S, 6.78
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| CAS # |
1448188-62-2
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| Related CAS # |
(R,S,S)-VH032; 2230826-33-0; (S,S,S)-VH032; 2097602-09-8; (S,R,R)-VH032; 2489876-59-5
|
| PubChem CID |
77232228
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
720
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(C)=O)=O)O)=O
|
| InChi Key |
GFVIEZBZIUKYOG-SVFBPWRDSA-N
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| InChi Code |
InChI=1S/C24H32N4O4S/c1-14-20(33-13-26-14)17-8-6-16(7-9-17)11-25-22(31)19-10-18(30)12-28(19)23(32)21(24(3,4)5)27-15(2)29/h6-9,13,18-19,21,30H,10-12H2,1-5H3,(H,25,31)(H,27,29)/t18-,19+,21-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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| Synonyms |
VH 032; VH-032; VH032; 1448188-62-2; N-Acetyl-3-Methyl-L-Valyl-(4r)-4-Hydroxy-N-[4-(4-Methyl-1,3-Thiazol-5-Yl)benzyl]-L-Prolinamide; (2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide; VH032
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~211.60 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1160 mL | 10.5798 mL | 21.1595 mL | |
| 5 mM | 0.4232 mL | 2.1160 mL | 4.2319 mL | |
| 10 mM | 0.2116 mL | 1.0580 mL | 2.1160 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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