CEP-18770
CEP-18770 is a novel, potent and reversible P2 threonine boronic acid inhibitor of proteasome that inhibits proteasome’s chymotrypsin-like activity, with the value of inhibition constant IC50 of 3.8 nM, by down-modulating the activity of nuclear factor-KB (NF-KB) as well as the expression of a few NF-KB downstream effectors. Preliminary results of multiple studies have shown that CEP-18770 exerts potent antitumor activities against human multiple myeloma (MM) cell lines by inducing apoptotic cell death, exhibits a strong antiangiogenic activity suppressing RANKL-induced osteoclastogenesis, and displays a favorable cytotoxicity profile towards normal cells including epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells.
Reference
Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008;111(5):2765-2775
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 413.3 |
| Cas No. | 847499-27-8 |
| Formula | C21H28BN3O5 |
| Solubility | insoluble in H2O; ≥16.75 mg/mL in DMSO; ≥32.27 mg/mL in EtOH with ultrasonic |
| Chemical Name | [(1R)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid |
| SDF | Download SDF |
| Canonical SMILES | B(C(CC(C)C)NC(=O)C(C(C)O)NC(=O)C1=CC=CC(=N1)C2=CC=CC=C2)(O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
RPMI-8226 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
40 nM, 4 to 8 hours |
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Applications |
As an inhibitor of proteasome, CEP-18770 induced an accumulation of ubiquitinated proteins over 4 to 8 hours with a pro?le similar to that observed after bortezomib (another proteasome inhibitor) treatment. |
| Animal experiment : [1] | |
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Animal models |
SCID mice bearing human MM RPMI 8226 subcutaneous xenograft |
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Dosage form |
Intravenous (from 1 to 6 mg/kg, 2q7d×8 injections) or oral administration (in a solution of 3% DMSO, 10% Solutol, and 87% sterile NaCl 0.9%, twice-a-week injections for 4 weeks at doses of 7.8, 10, 13 mg/kg in a volume of 20 mL/kg body weight of mouse). |
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Applications |
Intravenous administration of CEP-18770 exhibited sustained and dose-related tumor weight inhibition with RTWI of 100% at all tested doses. CEP-18770 also exhibited dose-related increases in the incidence of tumor-free mice by the completion of the studies (120 days after tumor transplantation) within the 3- and 4-mg/kg intravenous treatment groups, 89% and 80%, respectively. Oral administration of CEP-18770 resulted in a significant reduction of tumor weight and notable dose-related incidence of complete tumor regression (75% incidence of CR and 25% tumor-free mice at 10 mg/kg orally). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Piva R, Ruggeri B, Williams M, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood, 2008, 111(5): 2765-2775. |
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| Description | CEP-18770 is a novel orally-active inhibitor of the chymotrypsin-like activity of the proteasome with a cellular IC50 value of 3.8 nM. | |||||
| Targets | proteasome | |||||
| IC50 | 3.8 nM | |||||
Quality Control & MSDS
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Chemical structure
