Activity of the Novel BCR Kinase Inhibitor IQS019 in B-NHL
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Chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma and diffuse large B cell lymphoma represent various subtypes of B-cell lymphoid neoplasms with essential differences in cell origin, disease progression, and response to therapy. B-cell receptor (BCR) signaling has recently emerged as a central oncogenic pathway in these models, promoting tumor growth and survival. Here, we describe a new BCR-related kinase inhibitor, IQS019, which interacts with and efficiently prevents the activating phosphorylation of three apical BCR kinases (Syk, Lyn and Btk) in these models. Inhibiti...
Chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma and diffuse large B cell lymphoma represent various subtypes of B-cell lymphoid neoplasms with essential differences in cell origin, disease progression, and response to therapy. B-cell receptor (BCR) signaling has recently emerged as a central oncogenic pathway in these models, promoting tumor growth and survival. Here, we describe a new BCR-related kinase inhibitor, IQS019, which interacts with and efficiently prevents the activating phosphorylation of three apical BCR kinases (Syk, Lyn and Btk) in these models. Inhibition of BCR signaling by IQS019 leads to reduced cell proliferation, blockade of cell chemotaxis, and increased caspase-dependent apoptosis. Additionaly, in two different xenotransplant mouse models, treatment with IQS019 results in a remarkable decrease in BCR kinase phosphorylation and mitotic index, reduced tumor burden and tumor cell infiltration into the spleen. Altogether, these results warrant further investigation and clinical development of this novel BCR kinase inhibitor in mature B lymphoid malignancies.
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