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Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.
The results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity. Expand
Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase
Crystal structures of c-Abl show that the N-terminal myristoyl modification of c -Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Expand
Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571).
The inadvertent fusion of the bcr gene with the abl gene results in a constitutively active tyrosine kinase (Bcr-Abl) that transforms cells and causes chronic myelogenous leukemia. Small moleculeExpand
Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas.
Persistently activated or tyrosine-phosphorylated STAT3 (pSTAT3) is found in 50% of lung adenocarcinomas. pSTAT3 is found in primary adenocarcinomas and cell lines harboring somatic-activatingExpand
Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis.
The results show that chemical modification of a previously described JAK2 inhibitor results in the unexpected discovery of a novel DUB inhibitor with a unique antitumor mechanism. Expand
Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction.
It is demonstrated that pharmacologic inhibition of FAO with etomoxir or ranolazine inhibited proliferation and sensitized human leukemia cells to apoptosis induction by ABT-737, and evidence suggesting that FAO regulates the activity of Bak-dependent mitochondrial permeability transition is generated. Expand
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2.
It is demonstrated that fumagillin selectively inhibits the S. cerevisiae MetAP-2 protein in vivo, a metalloprotease, methionine aminopeptidase, that is highly conserved between human and Saccharomyces Cerevisiae and identified as an important target of study in the analysis of the potent biological activities of fumgillin. Expand
Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases
It is shown that cell-associated enveloped virions (CEV) use Abl- and Src-family tyrosine kinases for actin motility, and that these kinases act in a redundant fashion, perhaps permitting motility in a greater range of cell types. Expand
Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax).
It is shown that obatoclax potently induces apoptosis and decreases leukemia cell proliferation and may be used in a novel therapeutic strategy for AML alone and in combination with other targeted agents and chemotherapeutics. Expand
Pyridone 6, a pan-Janus-activated kinase inhibitor, induces growth inhibition of multiple myeloma cells.
Tetracyclic pyridone 6 is a more sensitive and specific inhibitor of JAK-STAT3 activity compared with AG490 and potently inhibited the growth of primaryMyeloma cells and myeloma-derived cell lines grown on BMSCs. Expand