Oleylamine-carbonyl-valinol inhibits auto-phosphorylation activity of native and T315I mutated Bcr-Abl, and exhibits selectivity towards oncogenic Bcr-Abl in SupB15 ALL cell lines
| Autor: | Nili Ruimi, Hazem Khamaisie, Soliman Khatib, J. Katzhendler, Jamal Mahajna, Yousef Najajreh, Martin Ruthardt |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Fusion Proteins
bcr-abl Molecular Conformation Molecular Dynamics Simulation Biology medicine.disease_cause Cell Line Tumor hemic and lymphatic diseases Genetics medicine Humans Amines Phosphorylation Kinase activity Protein Kinase Inhibitors neoplasms Molecular Biology Tumor Stem Cell Assay Mutation ABL Dose-Response Relationship Drug Kinase Myeloid leukemia Valine General Medicine Janus Kinase 2 Precursor Cell Lymphoblastic Leukemia-Lymphoma Molecular biology Fusion protein Molecular Docking Simulation Protein kinase domain Protein Binding |
| Zdroj: | Molecular Biology Reports. 40:2205-2213 |
| ISSN: | 1573-4978 0301-4851 |
| DOI: | 10.1007/s11033-012-2282-8 |
| Popis: | Chronic myeloid leukemia (CML) is characterized by the presence of p210(Bcr-Abl) which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of CML. Despite high rates of clinical response, CML patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein kinase domain. Previously, we have identified oleic acid as the active component in the mushroom Daedalea gibbosa that inhibited the kinase activity of Bcr-Abl. Here, we report that the oleyl amine derivatives, S-1-(1-Hydroxymethyl-2-methyl-propyl)-3-octadec-9-enyl-urea [oleylaminocarbonyl-L-N-valinol,oroleylaminocarbonyl-S-2-isopropyl-N-ethanolamine,oleylamine-carbonyl-L-valinol] (cpd 6) and R-1-(1-Hydroxymethyl-2-methyl-propyl)-3-octadec-9-enyl-urea [oleylamineocarbonyl-D-N-valinol, oleylaminocarbonyl-R-2-isopropyl-N-ethanolamine, or oleylamine-carbonyl-D-valinol] (cpd 7), inhibited the activity of the native and T315I mutated Bcr-Abl. Furthermore, cpd 6 and 7 exhibited higher activity towards the oncogenic Bcr-Abl in comparison to native c-Abl in SupB15 Ph-positive ALL cell line. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink