| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 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. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[2].
As a VHL-binding ligand-linker conjugate, this compound itself has no intrinsic biological activity; its function is to recruit the VHL E3 ubiquitin ligase complex after deprotection and conjugation to a target protein ligand. The trans-3-aminocyclobutanol and piperazine moieties provide rigidity and hydrophilicity, potentially optimizing ternary complex formation. The Boc-protected amine allows for selective deprotection under acidic conditions to reveal a free amine for amide bond formation with a target protein ligand. The terminal carboxylic acid can also be activated for conjugation. No specific in vitro degradation activity has been reported for this conjugate alone; it is a synthetic intermediate for PROTAC construction. |
| ln Vivo |
No specific in vivo activity has been reported for this conjugate alone; its in vivo degradation effects are observed only when incorporated into a complete PROTAC molecule. The in vivo efficacy of such a PROTAC would be evaluated in animal models of target-driven diseases.
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| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥98%. Its binding affinity to VHL is validated as part of a complete PROTAC construct using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
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| Cell Assay |
N/A; this conjugate is not tested alone in cell-based assays but is used as a building block for constructing VHL-recruiting PROTACs. In a typical PROTAC synthesis workflow, the Boc group is removed with TFA, and the resulting free amine is conjugated to a target protein ligand via amide bond formation using EDC/NHS or HATU. The terminal carboxylic acid can also be used for conjugation. The final PROTAC is then tested in target-expressing cells for degradation activity by Western blotting to determine the DC50.
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| Animal Protocol |
N/A; no animal studies are performed with the ligand-linker conjugate alone. For in vivo studies of a complete PROTAC, the molecule is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered via intraperitoneal (IP) or intravenous (IV) injection to animal models. Target degradation in tissues and tumor growth inhibition are monitored.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 825.03, a molecular formula of C42H60N6O9S, and a purity of ≥98%. It appears as a solid powder. For storage, it should be kept at -20degC, sealed, under nitrogen, away from moisture. It is soluble in DMSO. The Boc group is acid-labile, and the compound should be protected from strong acids. CAS: 2086301-47-3.
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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 is stable under recommended storage conditions. 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 |
[1]. Yimin Qian, et al. Compounds and methods for the targeted degradation of bromodomain-containing proteins. WO2017030814A1.
[2]. Nalawansha DA, et al. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-991. |
| Additional Infomation |
The trans-3-aminocyclobutanol ring introduces conformational rigidity into the linker, which can reduce entropic penalties upon ternary complex formation and potentially improve degradation potency and selectivity. The piperazine ring enhances water solubility and provides a basic nitrogen for protonation at physiological pH. This complex linker design is part of advanced PROTAC development for challenging targets. The compound is also known as VH032-Boc-trans-3-aminocyclobutanol-Pip-CH2COOH.
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| Molecular Formula |
C39H58N6O7S
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|---|---|
| Molecular Weight |
754.978828907013
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| Exact Mass |
754.408
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| CAS # |
2086301-47-3
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| PubChem CID |
126619795
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
53
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| Complexity |
1270
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| Defined Atom Stereocenter Count |
4
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| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)[C@H](C)NC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CN1CCC(CC1)OC1CC(C1)NC(=O)OC(C)(C)C)=O)=O)O)=O
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| InChi Key |
MBBHQLTUHKETEL-WQULMBDRSA-N
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| InChi Code |
InChI=1S/C39H58N6O7S/c1-23(25-9-11-26(12-10-25)33-24(2)40-22-53-33)41-35(48)31-19-28(46)20-45(31)36(49)34(38(3,4)5)43-32(47)21-44-15-13-29(14-16-44)51-30-17-27(18-30)42-37(50)52-39(6,7)8/h9-12,22-23,27-31,34,46H,13-21H2,1-8H3,(H,41,48)(H,42,50)(H,43,47)/t23-,27?,28+,30?,31-,34+/m0/s1
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| Chemical Name |
tert-butyl N-[3-[1-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethyl]piperidin-4-yl]oxycyclobutyl]carbamate
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~132.45 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (7.28 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 55.0 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: ≥ 5.5 mg/mL (7.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 55.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.31 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3245 mL | 6.6227 mL | 13.2454 mL | |
| 5 mM | 0.2649 mL | 1.3245 mL | 2.6491 mL | |
| 10 mM | 0.1325 mL | 0.6623 mL | 1.3245 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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