| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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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, (S,R,S)-AHPC-C1-Br itself has no intrinsic biological activity; its function is to recruit the VHL E3 ubiquitin ligase complex. The bromide group is a good leaving group that can undergo nucleophilic substitution (SN2) with nucleophiles such as thiols, amines, or carboxylates to attach a target protein ligand. 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 methylene (C1) linker provides the shortest possible spacer between the VHL ligand and the target ligand, which can be critical for target-E3 ligase pairs that require a minimal distance for ternary complex formation. (S,R,S)-AHPC (also known as VH032) is one of the most commonly used VHL ligands in PROTAC design due to its high affinity and well-characterized binding mode. |
| 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 IUPAC name is (2S,4R)-1-[(2S)-2-(2-bromoacetamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide.
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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 bromide group is displaced by a nucleophile from a target protein ligand (e.g., a thiol or amine) in the presence of a base such as K2CO3. 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 short methylene linker may be critical for achieving degradation activity for certain target proteins.
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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.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 551.50, a molecular formula of C24H31BrN4O4S, and a standard purity of ≥98%. The IUPAC name is (2S,4R)-1-[(2S)-2-(2-bromoacetamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide. It appears as a white to off-white solid powder. For storage, it should be kept long-term in a cool, dry place, sealed, away from moisture. It is soluble in DMSO. The product should be stored under nitrogen to prevent moisture absorption. CAS: 2379404-33-6.
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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 bromide group is reactive and should be handled with care to avoid premature reactions. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license. This compound is not an approved drug and has not been cleared for clinical use.
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| References | |
| Additional Infomation |
The methylene (C1) linker is the shortest possible spacer between the VHL ligand and the conjugated target protein ligand. This minimal spacer can be critical for target-E3 ligase pairs where a longer linker would prevent the formation of a productive ternary complex due to excessive flexibility or steric hindrance. The (S,R,S)-AHPC (VH032) VHL ligand is one of the most commonly used E3 ligase recruiters in PROTAC design due to its high affinity (Kd ~ 0.5-1 nM) and well-characterized binding mode. This conjugate enables the construction of highly compact VHL-based PROTACs with the shortest possible linker length, which can be valuable for structure-activity relationship studies and for targeting proteins with closely spaced binding sites.
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| Molecular Formula |
C24H31BRN4O4S
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|---|---|
| Molecular Weight |
551.496343851089
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| Exact Mass |
550.124
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| CAS # |
2379404-33-6
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| PubChem CID |
142596980
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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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 |
8
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| Heavy Atom Count |
34
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| Complexity |
741
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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)CBr)O
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| InChi Key |
YJWUYJKFKGUQHL-LVCYWYKZSA-N
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| InChi Code |
InChI=1S/C24H31BrN4O4S/c1-14-20(34-13-27-14)16-7-5-15(6-8-16)11-26-22(32)18-9-17(30)12-29(18)23(33)21(24(2,3)4)28-19(31)10-25/h5-8,13,17-18,21,30H,9-12H2,1-4H3,(H,26,32)(H,28,31)/t17-,18+,21-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[(2-bromoacetyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 :~125 mg/mL (~226.65 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8132 mL | 9.0662 mL | 18.1324 mL | |
| 5 mM | 0.3626 mL | 1.8132 mL | 3.6265 mL | |
| 10 mM | 0.1813 mL | 0.9066 mL | 1.8132 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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