| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
DC50: 0.47 nM (ZBTB16 in HT-1080 cells)[1]
CRBN (Cereblon), a substrate receptor for the CRL4 E3 ubiquitin ligase complex. |
|---|---|
| ln Vitro |
CC-3060 is a potent, efficacious, and dose-dependent promoter of CRBN-mediated ZBTB16 proteasomal degradation, exhibiting a DC50 of 0.47 nM in HT-1080 ZBTB16-ePL cells. It directly interacts with the C2H2 ZnF1 domain, forming a ternary complex with CRBN/ZBTB16. It also facilitates the degradation of other CRBN neo-substrates such as IKZF1, ZFP91, and ZNF276, while showing no effect on GSPT1 and CSNK1A1. CC-3060 promotes RARalpha-ZBTB16 fusion protein degradation (Ymin of 20 in RARalpha-ZBTB16-ePL cells).
|
| ln Vivo |
CC-3060 has demonstrated significant in vivo activity in a murine model of Clostridium difficile infection (CDI). Pharmacological degradation of ZBTB16 using CC-3060 significantly ameliorated colitis severity in this mouse model. This in vivo efficacy was achieved by reducing NLRP3 inflammasome activation and subsequent IL-1beta-dependent inflammatory signaling. Myeloid-specific Zbtb16 deficiency has also been shown to protect mice from C. difficile-induced colitis.
|
| Enzyme Assay |
Not applicable; CC-3060 is a complete cereblon modulator, not a synthetic intermediate. Its binding to CRBN is typically assessed using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The formation of a ternary complex with CRBN and ZBTB16 is a key metric of its activity and is often confirmed via functional in vitro ubiquitination assays or cellular degradation assays.
|
| Cell Assay |
The in vitro degradation activity of CC-3060 is evaluated in ZBTB16-expressing cell lines, such as HT-1080 ZBTB16-ePL cells. Cells are treated with increasing concentrations of CC-3060 (e.g., 1 pM to 10 uM) for a defined period, typically 4-24 hours. After treatment, cell lysates are prepared and ZBTB16 protein levels are measured by Western blotting or quantitative proteomics to determine the DC50 (half-maximal degradation concentration). The involvement of the proteasome and CRBN is confirmed by co-treatment with inhibitors like MG132 or CRBN knockdown.
|
| Animal Protocol |
For in vivo efficacy studies, CC-3060 is typically formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models of disease. In a murine model of Clostridium difficile infection (CDI), CC-3060 was administered to the animals, and colitis severity was assessed by measuring clinical parameters such as weight loss, colon length, and histological scoring. Inflammatory markers like IL-1beta production and ASC oligomerization were also measured to confirm target engagement and ZBTB16 degradation.
|
| ADME/Pharmacokinetics |
CC-3060 is a solid powder (purity ≥98% by HPLC). Its molecular formula is C22H17N3O5, and its molecular weight is 403.39. For storage, the powder can be kept at 4degC for up to 3 years, or at -20degC for longer storage. In a solvent (e.g., DMSO), it can be stored at -80degC for 6 months or at -20degC for 1 month. It is soluble in DMSO up to 40 mg/mL (99.16 mM, requiring ultrasonic and warming). For in vivo formulation, it is recommended to prepare a solution of 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. It has not been fully validated for medical applications. Standard chemical safety precautions should be followed during handling. Thalidomide-based compounds have known teratogenic effects, so this derivative should be handled with appropriate caution.
|
| References | |
| Additional Infomation |
CC-3060 is a second-generation Cereblon modulator classified as a CELMoD. It was identified in a chemical library screen as a compound that can target ZBTB16 for degradation via a distinct structural degron in ZnF1. This mechanism is unique as it degrades its target via a different zinc finger domain than earlier modulators like pomalidomide. It is a key chemical probe for studying ZBTB16 biology and has shown potential in pre-clinical models of colitis. It is not yet an approved therapeutic drug.
|
| Molecular Formula |
C22H17N3O5
|
|---|---|
| Molecular Weight |
403.39
|
| Exact Mass |
403.116
|
| CAS # |
444288-86-2
|
| PubChem CID |
21988575
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.6
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
30
|
| Complexity |
755
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NCC4=CC5=CC=CC=C5O4
|
| InChi Key |
GRICLJZNEMDVMA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H17N3O5/c26-18-9-8-16(20(27)24-18)25-21(28)14-5-3-6-15(19(14)22(25)29)23-11-13-10-12-4-1-2-7-17(12)30-13/h1-7,10,16,23H,8-9,11H2,(H,24,26,27)
|
| Chemical Name |
4-(1-benzofuran-2-ylmethylamino)-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.4790 mL | 12.3950 mL | 24.7899 mL | |
| 5 mM | 0.4958 mL | 2.4790 mL | 4.9580 mL | |
| 10 mM | 0.2479 mL | 1.2395 mL | 2.4790 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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