| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
IC50: 1.72 μM (p27Kip1 ubiquitination)[1]
CC0651 targets Cdc34A (also known as CDC34), an E2 ubiquitin-conjugating enzyme. It is an allosteric inhibitor that binds to Cdc34 and stabilizes the noncovalent Cdc34-ubiquitin complex. This disrupts the transfer of ubiquitin to target substrates, inhibiting the ubiquitination of proteins such as p27Kip1. |
|---|---|
| ln Vitro |
CC0651 significantly reduces the rate of ubiquitin chain initiation on substrates by SCFCdc4, as evaluated by the monoubiquitination of Sic1 by K0 ubiquitin. CC0651 really increases the synthesis of both ubiquitin dimers and monoubiquitinated hCdc34, which is consistent with the observed buildup of the hCdc34 conjugate in cells treated with the ester derivative of CC0651. CC0651 totally inhibits polyubiquitin chain assembly and reduces the generation of free triubiquitin and, to a lesser extent, hCdc34 monoubiquitin, while having no effect on diubiquitin production[1]. CC0651 is an inhibitor of the E2 ubiquitin conjugating enzyme Cdc34A. It works by trapping a weak contact between ubiquitin and the E2 donor ubiquitin binding site. A quantitative SCF ubiquitination assay with a β-Catenin substrate peptide reveals an IC50 of 18±1 μM for CC0651 inhibition, which is consistent with the effective doses seen in the NMR and TR-FRET assays[2].
CC0651 is a potent inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. It effectively inhibits the ubiquitination of p27Kip1 with an IC50 of 1.72 μM. As an allosteric inhibitor, it has a unique mechanism of action that stabilizes the Cdc34-ubiquitin complex. |
| ln Vivo |
Specific in vivo activity data for CC0651 is not extensively detailed in the available literature. As a research compound, its in vivo effects are primarily studied in the context of Cdc34 inhibition and its impact on the ubiquitin-proteasome system and cell cycle regulation. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic properties.
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| Enzyme Assay |
CC0651's activity as a Cdc34 inhibitor is assessed using in vitro ubiquitination assays. These assays measure the compound's ability to inhibit the ubiquitination of target substrates such as p27Kip1. The IC50 of 1.72 μM is determined from dose-response curves.
|
| Cell Assay |
PC-3 and HCT116 cell lines are grown in DMEM supplemented with Penicillin/Streptomycin, 2 mM glutamine, and 10% fetal bovine serum (FBS). Lentiviral shRNA constructs for human CDC34, UBE2R2, and nontarget control are used. For proliferation assays, PC-3 cultures are seeded at 5000 cells/well in quadruplicate in 24-well plates, grown for 24 hr, and then infected with lentiviral supernatant. For small-molecule inhibition, cells are seeded in quadruplicate at 500 cells/well in 96-well plates, grown for 24 hr, and treated with compound. Proliferation is measured by MTT assay. PC-3 or HCT 116 cultures are synchronized in G0/G1 by serum starvation for 30 hr and then released by addition of 10% serum. For epistasis experiments, PC-3 cells are infected with CDC34 shRNA for 24 hr, followed by addition of inhibitor and assessment of proliferation after 4 days. Anti-Cdc34, anti-p27, anti-α-tubulin, anti-ubiquitin, and anti-cyclin E antibodies are used[1]. |
| Animal Protocol |
In vivo animal model protocols for CC0651 would involve its administration to animal models to study the role of Cdc34 in the ubiquitin-proteasome system and cell cycle regulation. The compound's effects on protein degradation, cell cycle progression, and disease phenotypes would be assessed.
|
| ADME/Pharmacokinetics |
CC0651 has a molecular weight of 442.29 and a molecular formula of C20H21Cl2NO6. Specific pharmacokinetic data is not extensively detailed in the available literature. As a small molecule inhibitor, its pharmacokinetic properties would need to be evaluated in preclinical studies.
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| Toxicity/Toxicokinetics |
The toxicological profile of CC0651 has not been extensively characterized. As a research compound, it is intended for research use only and not for human consumption. Standard safety assessments would be required for clinical development.
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| References | |
| Additional Infomation |
CC0651 (CAS# 1319207-44-7) is a research compound used to study the ubiquitin-proteasome system and cell cycle regulation. It is an allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme with an IC50 of 1.72 μM for p27Kip1 ubiquitination. It is not approved for clinical use and is supplied as a research chemical.
|
| Molecular Formula |
C20H21CL2NO6
|
|---|---|
| Molecular Weight |
442.28
|
| Exact Mass |
441.075
|
| CAS # |
1319207-44-7
|
| PubChem CID |
53239927
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.531
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
29
|
| Complexity |
533
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
COCC(=O)N[C@@H](CC1=CC=C(C=C1)C2=CC(=CC(=C2)Cl)Cl)[C@@H]([C@H](C(=O)O)O)O
|
| InChi Key |
NTCBTNCWNRCBGX-YTQUADARSA-N
|
| InChi Code |
InChI=1S/C20H21Cl2NO6/c1-29-10-17(24)23-16(18(25)19(26)20(27)28)6-11-2-4-12(5-3-11)13-7-14(21)9-15(22)8-13/h2-5,7-9,16,18-19,25-26H,6,10H2,1H3,(H,23,24)(H,27,28)/t16-,18-,19+/m0/s1
|
| Chemical Name |
(2R,3S,4S)-5-[4-(3,5-dichlorophenyl)phenyl]-2,3-dihydroxy-4-[(2-methoxyacetyl)amino]pentanoic acid
|
| Synonyms |
CC 0651 CC-0651 CC0651
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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 |
| 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 : ≥ 56 mg/mL (~126.61 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 | 2.2610 mL | 11.3051 mL | 22.6101 mL | |
| 5 mM | 0.4522 mL | 2.2610 mL | 4.5220 mL | |
| 10 mM | 0.2261 mL | 1.1305 mL | 2.2610 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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