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Targeting Casein Kinase-1 and PI3K/AKT/mTOR Pathways for Treatment of c-Myc-Overexpressing Cancers, Organ Transplant Associated Complications and Autoimmune Diseases

机译：靶向酪蛋白激酶1和PI3K / AKT / mTOR途径治疗过度表达c-Myc的癌症，器官移植相关并发症和自身免疫性疾病

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摘要

The invention relates to the co-administration of select proteasome and PI3K inhibitors is useful for treating c-Myc-overexpressing cancers, particularly hematological cancers such as aggressive B- and T-cell lymphomas. In exemplified embodiments, coadministration of a dual PI3K/CK-1 inhibitor with a proteasome inhibitor synergistically increases cell death of aggressive B- and T-cell lymphomas as well as multiple myeloma over the individual or additive effect of either or both agents. This synergistic effect is associated with the previously unknown inhibition of the kinase casein kinase 1 epsilon (CK-1ε) by a PI3K inhibitor, such as TGR-1202. Accordingly, use of PI3K inhibitors that possess CK-1ε inhibition in combination with proteasome inhibitors provides a new therapy regime for treating c-Myc-overexpressing cancers, and particularly hematological cancers.

机译：本发明涉及选择性蛋白酶体和PI3K抑制剂的共同给药，其可用于治疗过度表达c-Myc的癌症，特别是血液学癌症，例如侵袭性B细胞和T细胞淋巴瘤。在示例性的实施方案中，双重PI3K / CK-1抑制剂与蛋白酶体抑制剂的共同施用协同增加了侵袭性B细胞和T细胞淋巴瘤以及多发性骨髓瘤的细胞死亡，超过了任一种或两种药物的单独或累加作用。这种协同作用与PI3K抑制剂（例如TGR-1202）对酪蛋白激酶1ε激酶（CK-1ε）的抑制作用未知。因此，具有CK-1ε抑制作用的PI3K抑制剂与蛋白酶体抑制剂的组合使用提供了一种新的治疗方案，用于治疗过度表达c-Myc的癌症，特别是血液学癌症。

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公开/公告号US2019070183A1

专利类型
公开/公告日2019-03-07

原文格式PDF
申请/专利权人 THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK;
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申请/专利号US201615773430
发明设计人 XIAOMING XU;LUIGI SCOTTO;OWEN OCONNOR;MICHAEL MANGONE;MARK LIPSTEIN;SHI-XIAN DENG;XAVIER O. JIRAU SERRANO;CHANGCHUN DENG;DONALD W. LANDRY;
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申请日2016-11-04
分类号A61K31/52;A61K31/551;A61P9/10;A61P35/02;A61K31/336;A61K31/5375;
国家 US
入库时间 2022-08-21 12:04:45

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