NPB001-05 Inhibits Bcr-Abl Kinase Leading to Apoptosis of Imatinib-Resistant Cells

Wagh, Vilas and Chile, Shailaja and Monahar, Sonal and Pal, Bikas C and Bandyopadhyay, Santu and Sharma, Somesh and Joshi, Kalpana (2011) NPB001-05 Inhibits Bcr-Abl Kinase Leading to Apoptosis of Imatinib-Resistant Cells. Frontiers in Bioscience. pp. 1273-1288.


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    The deregulated activity of the Bcr-Abl tyrosine kinase provides a rational basis for the development therapeutics in all phases of Chronic Myelogenous Leukemia (CML). Although a well studied imatinib therapy has clinical success against CML, resistance to imatinib due to mutations in the kinase domain, especially T315I poses a major problem for the ultimate success of CML therapy by this agent. Herein we describe an NPB001-05, derived from extract of Piper betle leafs, which is highly active in specifically inhibiting Bcr-Abl expressing cells. NPB001-05 inhibited the proliferation of BaF3 cells ectopically expressing wild type Bcr-Abl phenotype and 12 different imatinib-resistant mutations of clinical relevance (average IC50 5.7 μg/ml). Moreover, NPB001-05 was highly inhibitory to wild type P210Bcr-Abl and P210Bcr-Abl-T315I kinase activity and abrogated the autophosphorylating enzyme in time- and dose- dependent manner. NPB001-05 was non-toxic on normal cells, but was inhibitory to CML patient derived peripheral blood mononuclear cells. Treatment with NPB001-05 caused apoptosis induction and G0G1 cell cycle arrest in both Bcr- Abl wild type and T315I mutant cell lines

    Item Type: Article
    Subjects: Chemistry
    Infectious Diseases and Immunology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 13 Sep 2012 16:03
    Last Modified: 09 Jan 2013 15:46
    Official URL:

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