CC0651E2 enzyme inhibitor CAS# 1319207-44-7 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1319207-44-7 | SDF | Download SDF |
| PubChem ID | 53239927 | Appearance | Powder |
| Formula | C20H21Cl2NO6 | M.Wt | 442.29 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 56 mg/mL (126.61 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (2R,3S,4S)-5-[4-(3,5-dichlorophenyl)phenyl]-2,3-dihydroxy-4-[(2-methoxyacetyl)amino]pentanoic acid | ||
| SMILES | COCC(=O)NC(CC1=CC=C(C=C1)C2=CC(=CC(=C2)Cl)Cl)C(C(C(=O)O)O)O | ||
| Standard InChIKey | NTCBTNCWNRCBGX-YTQUADARSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Allosteric inhibitor of human Cdc34. Inhibits hCdc34-mediated ubiquitination of p27Kip1 (IC50 = 1.72 μM). Exhibits selectivity for hCdc34 over Uba1, Ube2G1, UbcH7, UbcH5, Ube2N (Ubc13), Ube2R2, SMURF2, SspH1 and Rnf168. |
CC0651 Dilution Calculator
CC0651 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.261 mL | 11.3048 mL | 22.6096 mL | 45.2192 mL | 56.524 mL |
| 5 mM | 0.4522 mL | 2.261 mL | 4.5219 mL | 9.0438 mL | 11.3048 mL |
| 10 mM | 0.2261 mL | 1.1305 mL | 2.261 mL | 4.5219 mL | 5.6524 mL |
| 50 mM | 0.0452 mL | 0.2261 mL | 0.4522 mL | 0.9044 mL | 1.1305 mL |
| 100 mM | 0.0226 mL | 0.113 mL | 0.2261 mL | 0.4522 mL | 0.5652 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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CC0651 is an allosteric inhibitor of Cdc34 ubiquitin-conjugating enzyme [1].
Ubiquitin-conjugating enzymes (E2 enzymes) are ubiquitin-carrier enzymes and perform the second step in the ubiquitin-proteasome system (UPS) that mediate the conjugation of ubiquitin to proteins for degradation. The E2 enzyme hCdc34 catalyzes the ubiquitination of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes [1].
CC0651 was an allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme and inhibited the ubiquitination of p27Kip1 with IC50 value of 1.72 μM. In human cancer cell lines PC-3, CC0651 inhibited cell proliferation with IC50 value of 20 μM and increased the level of p27Kip1. Also, CC0651 caused production of the hCdc34-ubiquitin conjugate [1]. CC0651 trapped a weak interaction between the E2 donor ubiquitin binding site and ubiquitin. CC0651-Cdc34A-ubiquitin complex reveals that CC0651 engaged a binding pocket formed from ubiquitin and Cdc34A. Also, CC0651 suppressed the spontaneous hydrolysis rate of the ubiquitin thioester-Cdc34A [2].
References:
[1]. Ceccarelli DF, Tang X, Pelletier B, et al. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell, 2011, 145(7): 1075-1087.
[2]. Huang H, Ceccarelli DF, Orlicky S, et al. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin. Nat Chem Biol, 2014, 10(2): 156-163.
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An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme.[Pubmed:21683433]
Cell. 2011 Jun 24;145(7):1075-87.
In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF(Skp2) substrate p27(Kip1). CC0651 does not affect hCdc34 interactions with E1 or E3 enzymes or the formation of the ubiquitin thioester but instead interferes with the discharge of ubiquitin to acceptor lysine residues. E2 enzymes are thus susceptible to noncatalytic site inhibition and may represent a viable class of drug target in the UPS.
E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin.[Pubmed:24316736]
Nat Chem Biol. 2014 Feb;10(2):156-163.
Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small-molecule inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester without decreasing the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities.
