A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL
نویسندگان
چکیده
منابع مشابه
Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr.
c-Abl tyrosine kinase is under rigorous control because of an unknown cellular inhibitor that maintains c-Abl in a relatively inactive state. Because SH2 domains are positive regulators of the nonreceptor tyrosine kinases, we tested whether this putative inhibitor would bind to an Abl SH2 protein construct and thus activate the c-Abl tyrosine kinase. Expression of a Mr 10,000 Abl SH2 protein in...
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Molecularly targeted kinase inhibitor cancer therapies are currently administered sequentially rather than simultaneously. We addressed the potential long-term impact of this strategy in patients with chronic myelogenous leukemia (CML), which is driven by the fusion oncogene BCR-ABL. Analysis of BCR-ABL genotypes in CML patients who relapsed after sequential treatment with the ABL inhibitors im...
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Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative appr...
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The Bcr-Abl fusion kinase drives oncogenesis in chronic myeloid leukemia (CML). CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib, which is effective in early stages of the disease. However, resistance to imatinib arises in later disease stages primarily because of a Bcr-Abl mutation. To gain deeper insight into Bcr-Abl signaling pathways, we generated phosphoty...
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In Ph(+) chronic myeloid leukemia (CML), the constitutively active Bcr-Abl kinase leads to the up-regulation and activation of multiple genes, which may subsequently result in the expression of leukemia-associated antigens. In this study, we investigated the immunogenicity of Bcr-Abl-regulated antigens by stimulating CD8(+) T lymphocytes with autologous dendritic cells transfected with RNA codi...
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ژورنال
عنوان ژورنال: ACS Chemical Biology
سال: 2020
ISSN: 1554-8929,1554-8937
DOI: 10.1021/acschembio.0c00348