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.
Mol Biol Rep
; 40(3): 2205-13, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23212614
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Valina
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Proteínas de Fusão bcr-abl
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Inibidores de Proteínas Quinases
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Mutação
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2013
Tipo de documento:
Article