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

dc.contributor.author Najajreh, Yousef
dc.contributor.author Khamaisie, Hazem
dc.contributor.author Ruimi, Nili
dc.contributor.author Khatib, Soliman
dc.contributor.author Katzhendler, Joshua
dc.contributor.author Ruthardt, Martin
dc.contributor.author Mahajna, Jamal
dc.date.accessioned 2018-09-03T10:42:14Z
dc.date.available 2018-09-03T10:42:14Z
dc.date.issued 2012-12-05
dc.description.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. en_US
dc.description.sponsorship This work was supported, in part, by DFG-RU 728/3-2 to MR, YN and JM. en_US
dc.identifier.issn 1573-4978
dc.identifier.uri https://dspace.alquds.edu/handle/20.500.12213/815
dc.language.iso en_US en_US
dc.publisher Springer en_US
dc.subject Oleylamine en_US
dc.subject L-/D-Valinol en_US
dc.subject Anti-tumor activity en_US
dc.subject Oleic acid en_US
dc.subject Bcr-Abl en_US
dc.subject Kinase en_US
dc.subject CML en_US
dc.title 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 en_US
dc.type Article en_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
RES_14_JOURNAL_paper_2.pdf
Size:
627.77 KB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description: