---------- Forwarded message ----------
From: Rob <[email protected]>
Date: Tue, 15 Feb 2005 22:32:47 -0600
Subject: [CMLHope] Comparative analysis of two clinically active
BCR-ABL kinase inhibitors reveals the role of conformation-specific
binding in resistance.
To: [EMAIL PROTECTED]


Structural studies suggest that most point mutations in the BCR-ABL
kinase domain cause resistance to the ABL kinase inhibitor imatinib by
impairing the flexibility of the kinase domain, restricting its
ability to adopt the inactive conformation required for optimal
imatinib binding, rather than by directly interfering with drug
contact residues. BMS-354825, currently in clinical development for
imatinib-resistant chronic myelogenous leukemia, is a dual SRC/ABL
kinase inhibitor that binds ABL in both the active and inactive
conformation.
 
http://cmlsupport.blogspot.com/2005/02/comparative-analysis-of-two-clinically.html


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