| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| Other Sizes |
| Targets |
VHL
VHL (von Hippel-Lindau), an E3 ubiquitin ligase. |
|---|---|
| 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. PROTACs target and selectively degrade target proteins by taking advantage of the intracellular ubiquitin-proteasome system.
As a VHL-binding ligand, VH032-OH itself has no intrinsic degradation activity; its function is to bind to the VHL E3 ubiquitin ligase with high affinity. When conjugated to a target protein ligand via a linker, the resulting PROTAC can recruit VHL to the target protein, leading to ubiquitination and proteasomal degradation. The free phenol group provides a handle for conjugation. |
| ln Vivo |
No specific in vivo activity has been reported for this ligand alone; its in vivo degradation activity is observed only when conjugated to a target protein ligand to form a complete PROTAC molecule. The in vivo efficacy of such a PROTAC is typically evaluated in animal models.
|
| Enzyme Assay |
N/A; as a ligand, its binding affinity to VHL is typically determined using biophysical methods such as surface plasmon resonance (SPR) or fluorescence polarization (FP) as part of the validation of the final PROTAC construct. The hydroxyl group can be used for further functionalization.
|
| Cell Assay |
N/A; this ligand is not evaluated alone in cell-based assays but is used as a building block to construct VHL-recruiting PROTACs for cellular degradation studies. In a typical conjugation step, the phenol or the carboxylic acid on the linker is activated and coupled to a target protein ligand.
|
| Animal Protocol |
N/A; no animal studies are performed with the ligand alone. In vivo efficacy studies would be conducted using the complete PROTAC molecule synthesized from this building block. The VHL ligand is cell-permeable and works effectively inside cells.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 488.60, a molecular formula of C24H32N4O5S, and appears as a white to light yellow solid powder. It is typically stored as a powder at -20degC for up to 3 years or in a solvent at -80degC for 6 months. The IUPAC name is (2S,4R)-1-((S)-2-acetamido-3,3-dimethylbutanoyl)-4-hydroxy-N-(2-hydroxy-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. LogP is 2.5, with 4 hydrogen bond donors and 7 acceptors.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. Standard chemical safety precautions should be followed during handling. The product should be stored in a sealed and protected environment (e.g., under nitrogen) to avoid moisture absorption.
|
| References | |
| Additional Infomation |
VH032 is one of the most commonly used VHL ligands in PROTAC design due to its high affinity and well-characterized binding mode. The hydroxylated derivative VH032-OH retains the high binding affinity of VH032 while providing a free phenol group that can be used for conjugation to target protein ligands without interfering with VHL binding. This compound is a crucial building block for the development of VHL-based PROTAC degraders.
|
| Molecular Formula |
C24H32N4O5S
|
|---|---|
| Molecular Weight |
488.5997
|
| Exact Mass |
488.209
|
| CAS # |
2244684-42-0
|
| PubChem CID |
142452655
|
| Appearance |
White to light yellow solid powder
|
| LogP |
2.5
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
760
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
CC1=C(SC=N1)C2=CC(=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)C)O)O
|
| InChi Key |
CUHVZPHLQIBKHX-LVCYWYKZSA-N
|
| InChi Code |
InChI=1S/C24H32N4O5S/c1-13-20(34-12-26-13)15-6-7-16(19(31)8-15)10-25-22(32)18-9-17(30)11-28(18)23(33)21(24(3,4)5)27-14(2)29/h6-8,12,17-18,21,30-31H,9-11H2,1-5H3,(H,25,32)(H,27,29)/t17-,18+,21-/m1/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-hydroxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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 (e.g. under nitrogen), 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)
|
| Solubility (In Vitro) |
DMSO :~50 mg/mL (~102.33 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.12 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 25.0 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: ≥ 2.5 mg/mL (5.12 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 25.0 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: ≥ 2.5 mg/mL (5.12 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 | 2.0467 mL | 10.2333 mL | 20.4666 mL | |
| 5 mM | 0.4093 mL | 2.0467 mL | 4.0933 mL | |
| 10 mM | 0.2047 mL | 1.0233 mL | 2.0467 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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