[CAS NO. 2070009-30-0] CEP-28122mesylatesalt
PRODUCTS SPECIFICATIONS [2070009-30-0]
DESCRIPTION [2070009-30-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 635.17 |
| Molecular Formula | C29H39ClN6O6S |
| SMILES | O=C([C@H]1[C@](C2)([H])C=C[C@]2([H])[C@H]1NC3=NC(NC4=CC=C5C(CC[C@@H](N6CCOCC6)CC5)=C4OC)=NC=C3Cl)N.O=S(C)(O)=O |
Summary
CEP-28122 mesylate salt, a diaminopyrimidine derivative, is a potent, selective, and orally bioavailable ALK inhibitor, with an IC 50 value of 1.9 nM for recombinant ALK kinase activity. CEP-28122 has antitumor activity in experimental models of ALK-positive human cancers. CEP-28122 mesylate salt has good pharmacodynamic and pharmacokinetic activity [1] .
In Vitro
CEP-28122 mesylate salt (3-3000 nM; 48 hours) treatment leads to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture, associates with concentration-related caspase 3/7 activation
[1]
.
CEP-28122 mesylate salt (30-1000 nM; 2 hours) treatment leads to substantial suppression of phosphorylation of putative downstream effectors of ALK in Sup-M2 cells, indicating that the downstream signaling pathways are mediated by individual ALK fusion protein
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay [1]
| Cell Line: | Karpas-299, Sup-M2, Toledo and HuT-102 cells |
| Concentration: | 10 nM, 100 nM, 1000 nM, 10000 nM |
| Incubation Time: | 48 hours |
| Result: | Treatment led to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture. |
Western Blot Analysis [1]
| Cell Line: | Sup-M2 cells |
| Concentration: | 30 nM, 100 nM, 300 nM, 1000 nM |
| Incubation Time: | 2 hours |
| Result: | Resulted in substantial suppression of phosphorylation of putative downstream effectors of ALK, including Stat-3, Akt, and ERK1/2 in Sup-M2 cells. |
In Vivo
CEP-28122 mesylate salt (3-30 mg/kg; oral gavage; twice a day; 12 days) produces dose-dependent antitumor activity in Sup-M2 subcutaneous tumor xenografts in SCID mice.In contrast, CEP-28122 has no antitumor activity in nu / nu mice bearing HCT116, suggesting that the antitumor activity of CEP-28122 in NPM-ALK–positive Sup-M2 tumor models is due to sustained NPM-ALK inhibition in tumors [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female SCID mice bearing Sup-M2 subcutaneous tumor xenografts and nu / nu mice bearing HCT116 aged 6-8 week old [1] |
| Dosage: | 3 mg/kg, 10 mg/kg and 30 mg/kg |
| Administration: | oral gavage; twice a day; 12 days |
| Result: | CEP-28122 produced dose-dependent antitumor activity in Sup-M2 subcutaneous tumor xenografts in SCID mice. In contrast, CEP-28122 had no antitumor activity in nu / nu mice bearing HCT116. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : ≥ 6.4 mg/mL ( 10.08 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5744 mL | 7.8719 mL | 15.7438 mL |
| 5 mM | 0.3149 mL | 1.5744 mL | 3.1488 mL |
| 10 mM | 0.1574 mL | 0.7872 mL | 1.5744 mL |