| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
VHL
VHL (von Hippel-Lindau), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
As a VHL-binding ligand, VHL Ligand 8 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 (e.g., an androgen receptor (AR) ligand) via an appropriate linker, the resulting PROTAC (ARD-266) can simultaneously bind to both the target protein (AR) and VHL, leading to ubiquitination and subsequent proteasomal degradation of the target protein. The high potency of ARD-266 (DC50 = 0.2-1 nM in AR-positive LNCaP cells) demonstrates the effectiveness of this VHL ligand in PROTAC applications.
|
| 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. ARD-266 has been developed for the treatment of prostate cancer, and its in vivo efficacy has been evaluated in preclinical 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 isothermal titration calorimetry (ITC) as part of the validation of the final PROTAC construct. The compound is used as a synthetic intermediate. The purity of the compound is typically confirmed by HPLC, with a standard purity of ≥98%. 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.
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| 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. In the synthesis of ARD-266, this VHL ligand is conjugated to an AR-targeting ligand via a linker. The resulting PROTAC is then tested in AR-positive prostate cancer cells (e.g., LNCaP) for degradation activity by Western blotting to determine the DC50. ARD-266 has been reported to degrade AR with a DC50 of 0.2-1 nM in LNCaP cells, demonstrating the high potency of this VHL ligand.
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| Animal Protocol |
N/A; no animal studies are performed with the ligand alone. For in vivo studies of ARD-266, the complete PROTAC molecule is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models (e.g., mouse xenografts of prostate cancer) via intraperitoneal (IP) or intravenous (IV) injection. AR degradation in tumor tissues, tumor growth inhibition, and overall animal health are monitored.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 443.49, a molecular formula of C23H29N3O6, and a standard purity of ≥98%. It appears as a solid powder. For storage, it should be kept as a powder at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO. The product should be stored in a sealed container, protected from light. CAS: 2701565-76-4.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be followed during handling. The product has not been fully validated for medical applications. It is not an approved therapeutic drug and has not been cleared for clinical use. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.
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| References | |
| Additional Infomation |
VHL Ligand 8 is a key building block for the synthesis of ARD-266, a highly potent and VHL-based androgen receptor (AR) PROTAC degrader. ARD-266 has been developed for the treatment of castration-resistant prostate cancer (CRPC), a disease driven by AR signaling. This VHL ligand is part of a class of VHL-recruiting PROTACs that have shown great promise for targeting a wide range of disease-relevant proteins. The high affinity of this ligand for VHL (likely in the low nanomolar range) enables the construction of highly potent PROTACs with sub-nanomolar DC50 values. This compound is a valuable tool for developing VHL-based PROTACs for a variety of therapeutic targets.
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| Molecular Formula |
C23H29N3O6
|
|---|---|
| Molecular Weight |
443.492866277695
|
| Exact Mass |
443.205
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| CAS # |
2701565-76-4
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| PubChem CID |
145925677
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
681
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
CC1=NOC(=C1)[C@@H](C(C)C)C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@@H](CC(=O)O)C3=CC=CC=C3)O
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| InChi Key |
BYUIKERVKHGIMC-OEMYIYORSA-N
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| InChi Code |
InChI=1S/C23H29N3O6/c1-13(2)21(19-9-14(3)25-32-19)23(31)26-12-16(27)10-18(26)22(30)24-17(11-20(28)29)15-7-5-4-6-8-15/h4-9,13,16-18,21,27H,10-12H2,1-3H3,(H,24,30)(H,28,29)/t16-,17+,18+,21-/m1/s1
|
| Chemical Name |
(3S)-3-[[(2S,4R)-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic 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 (~225.48 mM)
H2O :~25 mg/mL (~56.37 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (112.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2548 mL | 11.2742 mL | 22.5484 mL | |
| 5 mM | 0.4510 mL | 2.2548 mL | 4.5097 mL | |
| 10 mM | 0.2255 mL | 1.1274 mL | 2.2548 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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