| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VHL (von Hippel-Lindau), an E3 ubiquitin ligase.
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|---|---|
| ln Vitro |
As a VHL-binding ligand-linker conjugate, (S,R,S)-AHPC-CO-C9-acid itself has no intrinsic biological activity; its function is to recruit the VHL E3 ubiquitin ligase complex. The terminal carboxylic acid is conjugated to a target protein ligand via amide bond formation using standard coupling reagents (e.g., EDC, HATU). The resulting PROTAC can simultaneously bind to both a target protein and VHL, leading to ubiquitination and subsequent proteasomal degradation of the target protein. The long C9 alkyl spacer provides extended flexibility and distance, which can be optimal for target proteins with binding sites that are far from the VHL recruitment site. The amide linkage may enhance stability. The (S,R,S)-AHPC (VH032) VHL ligand is one of the most commonly used E3 ligase recruiters in PROTAC design.
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| ln Vivo |
No specific in vivo activity has been reported for this conjugate 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 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). The C9 alkyl linker and amide bond can be characterized by mass spectrometry and NMR.
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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 PROTACs. In a typical conjugation step, the terminal carboxylic acid is activated with EDC and NHS and reacted with a primary amine-containing target protein ligand. The resulting PROTAC is then tested in target-expressing cancer cells for degradation activity by Western blotting to determine the DC50 (half-maximal degradation concentration). The long C9 alkyl linker may be critical for achieving degradation activity for certain target proteins where shorter linkers are ineffective.
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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 to animal models via intraperitoneal (IP) or intravenous (IV) injection. Target degradation in tissues and tumor growth inhibition are monitored. The long C9 spacer may improve the pharmacokinetic properties of the conjugate by enhancing flexibility and membrane permeability.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 694.92, a molecular formula of C38H54N4O6S, and a standard purity of ≥98%. The IUPAC name is (2S,4R)-1-((S)-2-acetamido-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-((4-(4-methylthiazol-5-yl)benzyl)amino)-1,9-dioxo-9-((9-oxo-9-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)nonyl)amino)nonan-4-yl)pyrrolidine-2-carboxamide? This is complex. For storage, it should be kept as a solid 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 under an inert atmosphere. CAS: 2172819-78-0.
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| 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 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 | |
| Additional Infomation |
The long C9 alkyl linker (nine-carbon chain) provides an extended, flexible, and hydrophobic spacer that can be optimal for target-E3 ligase pairs requiring a long distance between binding sites. The amide bond within the linker introduces a polar, rigid element that may enhance metabolic stability and reduce aggregation compared to purely hydrophobic alkyl linkers. This conjugate is a valuable building block for developing VHL-recruiting PROTACs with optimized linker lengths for specific target proteins. The terminal carboxylic acid enables direct conjugation to target protein ligands via standard amide coupling.
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| Molecular Formula |
C33H48N4O6S
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|---|---|
| Molecular Weight |
628.822427749634
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| Exact Mass |
628.329
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| CAS # |
2172819-78-0
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| PubChem CID |
134184031
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| Appearance |
White to off-white solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
44
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| Complexity |
951
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| Defined Atom Stereocenter Count |
3
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| 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)CCCCCCCCCC(=O)O)O
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| InChi Key |
MTQZLQCVZFDQOZ-DIIXFEDBSA-N
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| InChi Code |
InChI=1S/C33H48N4O6S/c1-22-29(44-21-35-22)24-16-14-23(15-17-24)19-34-31(42)26-18-25(38)20-37(26)32(43)30(33(2,3)4)36-27(39)12-10-8-6-5-7-9-11-13-28(40)41/h14-17,21,25-26,30,38H,5-13,18-20H2,1-4H3,(H,34,42)(H,36,39)(H,40,41)/t25-,26+,30-/m1/s1
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| Chemical Name |
11-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-11-oxoundecanoic 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~159.03 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (7.95 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 50.0 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 mg/mL (7.95 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 50.0 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: ≥ 5 mg/mL (7.95 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 | 1.5903 mL | 7.9514 mL | 15.9028 mL | |
| 5 mM | 0.3181 mL | 1.5903 mL | 3.1806 mL | |
| 10 mM | 0.1590 mL | 0.7951 mL | 1.5903 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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