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

Date
2012-12-05
Authors
Najajreh, Yousef
Khamaisie, Hazem
Ruimi, Nili
Khatib, Soliman
Katzhendler, Joshua
Ruthardt, Martin
Mahajna, Jamal
Journal Title
Journal ISSN
Volume Title
Publisher
Springer
Abstract
Chronic myeloid leukemia (CML) is characterized by the presence of p210Bcr-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-Nvalinol, 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.
Description
Keywords
Oleylamine, L-/D-Valinol, Anti-tumor activity, Oleic acid, Bcr-Abl, Kinase, CML
Citation