| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PROTAC-VHL-ligand targets the Von Hippel-Lindau (VHL) protein, which is the substrate-recognition component of an E3 ubiquitin ligase complex. By binding to VHL with high affinity, this ligand serves as a "handle" to recruit the ubiquitin-proteasome system to a protein of interest when incorporated into a PROTAC molecule. The VHL protein is part of the VCB complex (VHL-Elongin B-Elongin C-Cullin 2), which is responsible for the ubiquitination of hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions.
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| ln Vitro |
As a standalone VHL ligand, PROTAC-VHL-ligand does not exhibit direct enzymatic inhibitory activity or receptor modulation. Its in vitro activity is defined by its ability to bind to the VHL protein with high affinity, which is characterized by a dissociation constant (Kd) in the low nanomolar to micromolar range. When incorporated into a PROTAC, its in vitro activity is evaluated by the efficiency of targeted protein degradation, typically measured by Western blot or quantitative proteomics.
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| ln Vivo |
PROTAC-VHL-ligand is not a therapeutic agent and does not have direct in vivo biological activity. Its in vivo activity is determined by the PROTAC molecules that incorporate this ligand. When used as part of a PROTAC, the resulting molecule can induce the degradation of target proteins in vivo, leading to modulation of disease-relevant pathways. The in vivo efficacy of VHL-based PROTACs has been demonstrated in various xenograft models.
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| Enzyme Assay |
In vitro binding assays for PROTAC-VHL-ligand typically involve surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure its affinity for the VHL protein. In a typical SPR assay, the VHL protein is immobilized on a sensor chip, and varying concentrations of the ligand are passed over the surface. The resulting sensorgrams are fitted to a 1:1 binding model to calculate the association rate (ka), dissociation rate (kd), and equilibrium dissociation constant (KD).
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| Cell Assay |
In vitro cell-based assays for PROTAC-VHL-ligand are not typically performed on the ligand itself, as it lacks degradation activity. Instead, the activity is assessed using the final PROTAC molecule that incorporates this VHL ligand. Cells are treated with the PROTAC at various concentrations, and the levels of the target protein are measured by Western blot or ELISA to determine the DC50 (concentration for 50% degradation) and Dmax (maximum degradation).
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| Animal Protocol |
In vivo animal studies for PROTAC-VHL-ligand are conducted using the PROTAC molecules that incorporate this ligand, rather than the ligand alone. Typical protocols involve administering the PROTAC to mice via intravenous, intraperitoneal, or oral routes. Tumor growth inhibition is assessed in xenograft models, and pharmacodynamic studies measure target protein degradation in tumor tissue by immunohistochemistry or Western blot.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of PROTAC-VHL-ligand are not extensively characterized, as it is a research tool rather than a therapeutic agent. When incorporated into PROTACs, the pharmacokinetic properties are determined by the overall PROTAC molecule, including its molecular weight (typically >800 Da), lipophilicity, and metabolic stability. VHL-based PROTACs generally exhibit moderate to good oral bioavailability and tissue distribution.
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| Toxicity/Toxicokinetics |
PROTAC-VHL-ligand is considered a laboratory reagent with low inherent toxicity. It is not intended for human or veterinary therapeutic use. Standard safety precautions should be followed when handling this compound. It is supplied with a purity of ≥98% and should be stored as a powder at -20°C for long-term stability.
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| References |
ACS Chem Biol.2015 Aug 21;10(8):1831-7.
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| Additional Infomation |
PROTAC-VHL-ligand is a research-grade compound used as a VHL ligand for PROTAC synthesis. It is also known as (S,R,S)-AHPC and VH032-NH2. Its molecular formula is C₂₂H₃₀N₄O₃S, and it is soluble in DMSO. This product is for research use only and is not for human or veterinary therapeutic use.
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| Molecular Formula |
C22H30N4O3S
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|---|---|
| Molecular Weight |
430.564
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| Exact Mass |
430.203
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| Elemental Analysis |
C, 61.37; H, 7.02; N, 13.01; O, 11.15; S, 7.45
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| CAS # |
1448297-52-6
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| Related CAS # |
1448297-52-6;1448189-80-7 (HCl);
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| PubChem CID |
89702519
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
691.6±55.0 °C at 760 mmHg
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| Flash Point |
372.1±31.5 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.604
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| LogP |
0.85
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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 |
6
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| Heavy Atom Count |
30
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| Complexity |
618
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C1=NC(C)=C(C2C=CC(CNC(=O)[C@@H]3C[C@@H](O)CN3C(=O)C(N)C(C)(C)C)=CC=2)O1
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| InChi Key |
ZLOXMSNKPDWMEF-ZIFCJYIRSA-N
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| InChi Code |
InChI=1S/C22H30N4O3S/c1-13-18(30-12-25-13)15-7-5-14(6-8-15)10-24-20(28)17-9-16(27)11-26(17)21(29)19(23)22(2,3)4/h5-8,12,16-17,19,27H,9-11,23H2,1-4H3,(H,24,28)/t16-,17+,19-/m1/s1
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| Chemical Name |
(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
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| Synonyms |
VHL-7526 TFA; VHL-7526; PROTAC-VHL-ligand; Protein degrader 1 TFA; VH032-NH2 TFA; VHL ligand 1 TFA; Protein degrader 1 TFA , VHL7526; VHL 7526 trifluoroacetic acid
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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 |
| 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 (~232.26 mM)
H2O : ≥ 25 mg/mL (~58.06 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.81 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 (5.81 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 (5.81 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 | 2.3226 mL | 11.6128 mL | 23.2256 mL | |
| 5 mM | 0.4645 mL | 2.3226 mL | 4.6451 mL | |
| 10 mM | 0.2323 mL | 1.1613 mL | 2.3226 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.
Products are for research use only; We do not sell to patients
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