Cancer Cell 2005,
PMID: 15710326
Weisberg, Ellen; Manley, Paul W; Breitenstein, Werner; Brüggen, Josef; Cowan-Jacob, Sandra W; Ray, Arghya; Huntly, Brian; Fabbro, Doriano; Fendrich, Gabriele; Hall-Meyers, Elizabeth; Kung, Andrew L; Mestan, Jürgen; Daley, George Q; Callahan, Linda; Catley, Laurie; Cavazza, Cara; Azam, Mohammad; Mohammed, Azam; Neuberg, Donna; Wright, Renee D; Gilliland, D Gary; Griffin, James D
The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We describe a novel selective inhibitor of Bcr-Abl, AMN107 (IC50 <30 nM), which is significantly more potent than imatinib, and active against a number of imatinib-resistant Bcr-Abl mutants. Crystallographic analysis of Abl-AMN107 complexes provides a structural explanation for the differential activity of AMN107 and imatinib against imatinib-resistant Bcr-Abl. Consistent with its in vitro and pharmacokinetic profile, AMN107 prolonged survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolonged survival in imatinib-resistant CML mouse models. AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL.
Diseases/Pathways annotated by Medline MESH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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Text Mining Data
Bcr-Abl ⊣ AMN107: "
Characterization of
AMN107 , a selective
inhibitor of native and mutant
Bcr-Abl
"
Bcr-Abl ⊣ AMN107: "
Characterization of AMN107 , a selective inhibitor of native and mutant Bcr-Abl
"
Manually curated Databases
No curated data.