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CEP-28122

Cat. No. M1946
CEP-28122 Structure
Size Price Availability Quantity
10mg USD 350 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

CEP-28122 is a potent inhibitor of recombinant ALK activity and cellular ALK tyrosine phosphorylation. CEP-28122 induced concentration-dependent growth inhibition/cytotoxicity of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cells, and displayed dose-dependent inhibition of ALK tyrosine phosphorylation in tumor xenografts in mice. CEP-28122 displayed marginal antitumor activity against ALK-negative human tumor xenografts under the same dosing regimens. Administration of CEP-28122 was well tolerated in mice and rats. In summary, CEP-28122 is a highly potent and selective orally active ALK inhibitor with a favorable pharmaceutical and pharmacokinetic profile and robust and selective pharmacologic efficacy against ALK-positive human cancer cells and tumor xenograft models in mice.

Protocol
Cell Experiment
Cell lines NPM-ALK–positive ALCL (Karpas-299 and Sup-M2) cells and ALK-negative lymphoma HuT-102 and leukemia Toledo cells; EML4-ALK–positive (NCI-H2228 and H3122) and EML4-ALK–negative (NCI-H1650) NSCLC cells and neuroblastoma cell lines
Preparation method Cell growth inhibition
Living cells were measured with the CellTiter 96 nonradioactive cell proliferation assay (MTS assay) kit. In brief, the cells were seeded on 96-well plates and 48 to 72 hours after compound treatment, equal volume of reagents from the kit was added to the culture medium. After incubation for 1 to 4 hours, the plates were measured with a plate reader and the relative cell numbers were calculated on the basis of the standard curve.
Concentrations 0~10 μ M
Incubation time 48 to 72 h
Animal Experiment
Animal models SCID mice bearing NCI-H2228, NCI-H3122, and NCI-1650 (A) or NB-1 and NB-1691 (B) subcutaneous tumor xenografts
Formulation PEG-400, or dH2O
Dosages 3, 10, or 30 mg/kg twice a day for 10 days
Administration oral
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 539.07
Formula C28H35ClN6O3
CAS Number 1022958-60-6
Purity >99%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Mol Cancer Ther (2012). Figure 2. CEP-28122
Method MTS assays
Cell Lines NPM-ALK–positive ALCL (Karpas-299 and Sup-M2) cells
Concentrations 30, 100, 300 and 1,000 nmol/L
Incubation Time 48 h
Results The activity of growth inhibition and caspase activation are consistent with the cellular inhibition of NPM-ALK phosphorylation. In contrast, CEP-28122 had no-to-marginal growth inhibition and did not induce significant caspase 3/7 activation in ALK-negative leukemia Toledo and lymphoma HuT-102 cells at concentrations up to 3,000 nmol/L
Rating
Source Mol Cancer Ther (2012). Figure 1. CEP-28122
Method immunoblot analysis
Cell Lines NSCLC NCI-H2228 and NCI-H3122 cells
Concentrations 30, 100, 300 and 1,000 nmol/L
Incubation Time 2 h
Results In a cellular phosphorylation assay, treatment of NPMALK–positive ALCL cells, Sup-M2 and Karpas-299, with CEP-28122 led to concentration-related inhibition of NPM-ALK tyrosine (664) phosphorylation, with calculated cellular IC50 values of 20 to 30 nmol/L
Rating
References

CEP-28122, a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers.
Cheng M, et al. Mol Cancer Ther. 2012 Mar;11(3):670-9. PMID: 22203728.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: CEP-28122 supplier, ALK, inhibitors

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