| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cereblon 1.5 nM (DC50)
CRBN (cereblon); VHL (von Hippel-Lindau) E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
CRBN-6-5-5-VHL exhibits potent in vitro degradation of cereblon with a DC50 of 1.5 nM in MM1S cells. It selectively degrades CRBN without affecting neo-substrates IKZF1 and IKZF3, demonstrating excellent selectivity. The compound is cell-permeable and effective at low nanomolar concentrations.
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| ln Vivo |
No specific in vivo activity has been reported for this degrader; as a potent cereblon degrader, it is expected to have significant in vivo effects in relevant disease models. Further preclinical studies are ongoing for this research compound.
|
| Enzyme Assay |
N/A; as a complete PROTAC molecule, its binding to both CRBN and VHL can be assessed using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to determine binding affinities and ternary complex formation. The cereblon degradation activity is typically confirmed by functional cellular assays.
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| Cell Assay |
The in vitro degradation activity of CRBN-6-5-5-VHL is evaluated in MM1S multiple myeloma cells. Cells are treated with increasing concentrations of the compound (e.g., 0.1 nM to 1 uM) for 4-24 hours. After treatment, cell lysates are prepared and CRBN protein levels are measured by Western blotting or quantitative proteomics to determine DC50 values. Neo-substrate levels (IKZF1/IKZF3) are also assessed to confirm selectivity.
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| Animal Protocol |
N/A; in vivo efficacy studies for CRBN-6-5-5-VHL would typically be conducted in mouse xenograft models of multiple myeloma or other CRBN-dependent cancers. The compound would be 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. Tumor growth inhibition, CRBN degradation in tumor tissue, and overall animal health would be monitored.
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| ADME/Pharmacokinetics |
The compound has a molecular weight of 972.21, a molecular formula of C51H69N7O10S, and is soluble in DMSO. It is typically stored as a powder at -20degC for up to 3 years or in a solvent at -80degC for 6 months. The product appears as a yellow solid powder and requires protection from light during storage.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or clinical use. Standard safe handling practices for laboratory chemical reagents should be followed. PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
|
| References | |
| Additional Infomation |
CRBN-6-5-5-VHL is a unique PROTAC molecule that targets and degrades the E3 ligase cereblon itself rather than a traditional disease-relevant target. This tool compound is valuable for studying cereblon biology and validating it as a therapeutic target. It is not a therapeutic drug and has not been approved for clinical use.
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| Molecular Formula |
C51H69N7O10S
|
|---|---|
| Molecular Weight |
972.19947218895
|
| Exact Mass |
971.482
|
| CAS # |
2362575-45-7
|
| PubChem CID |
145874883
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.6
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| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
27
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| Heavy Atom Count |
69
|
| Complexity |
1740
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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)CCCCOCCCCCOCCCCCCNC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)O
|
| InChi Key |
LIMCHOLAKDUZDS-XARBDFOFSA-N
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| InChi Code |
InChI=1S/C51H69N7O10S/c1-33-44(69-32-54-33)35-20-18-34(19-21-35)30-53-46(62)40-29-36(59)31-57(40)50(66)45(51(2,3)4)55-41(60)17-8-13-28-68-27-12-7-11-26-67-25-10-6-5-9-24-52-38-16-14-15-37-43(38)49(65)58(48(37)64)39-22-23-42(61)56-47(39)63/h14-16,18-21,32,36,39-40,45,52,59H,5-13,17,22-31H2,1-4H3,(H,53,62)(H,55,60)(H,56,61,63)/t36-,39?,40+,45-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[5-[5-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexoxy]pentoxy]pentanoylamino]-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: 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) |
DMSO :~113.33 mg/mL (~116.57 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 | 1.0286 mL | 5.1430 mL | 10.2859 mL | |
| 5 mM | 0.2057 mL | 1.0286 mL | 2.0572 mL | |
| 10 mM | 0.1029 mL | 0.5143 mL | 1.0286 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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