All AbMole products are for research use only, cannot be used for human consumption.
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.
 |
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 |
 |
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 |
| 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 |
| Molecular Weight | 539.07 |
| Formula | C28H35ClN6O3 |
| CAS Number | 1022958-60-6 |
| Solubility (25°C) | DMF: 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related ALK Products |
|---|
| F-1
F-1 is a potent ALK and ROS1 dual inhibitor, suppresses phospho-ALK and its relative downstream signaling pathways, with IC50 values of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM for ALKWT, ROS1WT, ALKL1196M and ALKG1202R, respectively. |
| TL13-22
TL13-22 is a negative control for TL13-12 and a potent ALK inhibitor with an IC50 of 0.54 nM. |
| TL13-110
TL13-110 is a negative control for TL13-112 and a potent ALK inhibitor with an IC50 of 0.34 nM. |
| ALK inhibitor 2
ALK inhibitor 2 is a potent pyrimidin ALK inhibitor. |
| NVL-655 TFA
NVL-655 (ALK-IN-27) TFA is a novel, brain-permeable, selective ALK inhibitor with antitumor activity. For Ba/F3 CLIP1-LTK cells, NVL-655 (ALK-IN-27) TFA has an IC50 of 2.7 nM. It can be used in studies related to ALK-positive non-small cell lung cancer (NSCLC). |
All AbMole products are for research use only, cannot be used for human consumption or veterinary use. We do not provide products or services to individuals. Please comply with the intended use and do not use AbMole products for any other purpose.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2024 AbMole BioScience. All Rights Reserved.
