| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
E3 ligase Ligand 1 targets the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. By binding to VHL, it recruits the E3 ligase to target proteins that are fused to a ligand for the protein of interest in PROTAC molecules, leading to ubiquitination and proteasomal degradation of the target protein.
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|---|---|
| ln Vitro |
E3 ligase Ligand 1 binds to VHL with high affinity and selectivity. It serves as a critical building block in the development of PROTACs, a novel therapeutic modality designed to selectively eliminate disease-causing proteins. It is used to synthesize ARV-771, a VHL E3 ligase-based BET PROTAC.
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| ln Vivo |
In vivo activity is not applicable for E3 ligase Ligand 1 itself, as it is a building block for PROTACs rather than a therapeutic agent. Its activity is evaluated as part of PROTAC molecules that incorporate this ligand to target specific proteins for degradation in vivo.
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| Enzyme Assay |
Cell-free assays for E3 ligase Ligand 1 include binding affinity measurements using surface plasmon resonance or isothermal titration calorimetry with purified VHL protein. Competition binding assays using fluorescently labeled ligands can also be performed. The compound's binding affinity and selectivity for VHL over other E3 ligases are characterized.
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| Cell Assay |
Cells expressing the target protein of interest (e.g., BET proteins for ARV-771) are treated with PROTAC molecules that incorporate E3 ligase Ligand 1. Target protein degradation is assessed by Western blot. Cell proliferation, viability, and apoptosis assays are performed to evaluate functional consequences of target degradation. The compound itself is not used directly in cellular assays.
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| Animal Protocol |
In vivo animal studies are performed with PROTAC molecules that incorporate E3 ligase Ligand 1, not with the ligand itself. The PROTAC is administered via various routes in rodent xenograft or disease models. Target protein degradation in tumor or tissue samples is assessed by Western blot or immunohistochemistry. Efficacy endpoints depend on the specific disease model and target protein.
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| ADME/Pharmacokinetics |
E3 ligase Ligand 1 is a small molecule (MW 481.05, formula C23H33ClN4O3S) with favorable physicochemical properties for use in PROTAC design. It is cell-permeable and soluble in DMSO. The compound is stored at -20°C. Detailed PK parameters are not applicable as the ligand itself is not administered as a therapeutic.
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| Toxicity/Toxicokinetics |
Toxicity data for E3 ligase Ligand 1 are limited as it is a research building block for PROTACs rather than a therapeutic agent. The compound is handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
E3 ligase Ligand 1 (molecular formula C23H33ClN4O3S, MW 481.05) is also known as (S,R,S)-AHPC-Me hydrochloride. It is a synthetic, cell-permeable ligand for the VHL E3 ubiquitin ligase that serves as a critical building block in PROTAC development. It is used to synthesize ARV-771, a VHL E3 ligase-based BET PROTAC. The compound is intended for research use only.
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| Molecular Formula |
C23H33CLN4O3S
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|---|---|
| Molecular Weight |
481.051123380661
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| Exact Mass |
480.196
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| CAS # |
1948273-03-7
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| PubChem CID |
122422950
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| Appearance |
Off-white to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
647
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| Defined Atom Stereocenter Count |
4
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| SMILES |
N[C@@H](C(C)(C)C)C(N1[C@H](C(N[C@@H](C)C2=CC=C(C3=C(C)N=CS3)C=C2)=O)C[C@@H](O)C1)=O.Cl
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| InChi Key |
GHFOLQCCYGBOTL-QDVBFIRISA-N
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| InChi Code |
InChI=1S/C23H32N4O3S.ClH/c1-13(15-6-8-16(9-7-15)19-14(2)25-12-31-19)26-21(29)18-10-17(28)11-27(18)22(30)20(24)23(3,4)5;/h6-9,12-13,17-18,20,28H,10-11,24H2,1-5H3,(H,26,29);1H/t13-,17+,18-,20+;/m0./s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide;hydrochloride
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| Synonyms |
E3 ligase Ligand-1; E3 ligase Ligand1; E3 ligase Ligand 1
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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, 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) |
H2O : ~100 mg/mL (~207.88 mM)
DMSO : ≥ 63 mg/mL (~130.96 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 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 20.8 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: 2.08 mg/mL (4.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (207.88 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0788 mL | 10.3939 mL | 20.7879 mL | |
| 5 mM | 0.4158 mL | 2.0788 mL | 4.1576 mL | |
| 10 mM | 0.2079 mL | 1.0394 mL | 2.0788 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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