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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

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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-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.

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Acknowledgments

This work was supported, in part, by DFG-RU 728/3-2 to MR, YN and JM.

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Authors and Affiliations

  1. Anticancer Drugs Research Lab, Faculty of Pharmacy, Al-Quds University, Jerusalem-Abu Dies, P.O. Box 20002, Palestine

    Yousef Najajreh

  2. Cancer Drug Discovery Program, Migal-Galilee Technology Center, P.O. Box 831, 11016, Kiryat Shmona, Israel

    Hazem Khamaisie, Nili Ruimi & Jamal Mahajna

  3. Oxidative Stress Research Laboratory, MIGAL-Galilee Technology Center, 11016, Kiryat Shmona, Israel

    Soliman Khatib

  4. Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, 91120, Jerusalem, Israel

    Joshua Katzhendler

  5. Laboratory for Tumor Stem Cell Biology, Department of Hematology, J.W. Goethe University, Frankfurt, Germany

    Martin Ruthardt

  6. Department of Nutritional Sciences, Tel-Hai College, Kiryat Shmona, Israel

    Jamal Mahajna

Authors
  1. Yousef Najajreh
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  2. Hazem Khamaisie
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  3. Nili Ruimi
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  4. Soliman Khatib
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  5. Joshua Katzhendler
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  6. Martin Ruthardt
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  7. Jamal Mahajna
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Correspondence to Jamal Mahajna.

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Najajreh, Y., Khamaisie, H., Ruimi, N. et al. 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, 2205–2213 (2013). https://doi.org/10.1007/s11033-012-2282-8

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  • DOI: https://doi.org/10.1007/s11033-012-2282-8

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