Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells

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Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells

Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences ...

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Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer.

Glutamine serves as an important source of energy and building blocks for many tumor cells. The first step in glutamine utilization is its conversion to glutamate by the mitochondrial enzyme glutaminase. CB-839 is a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KGA and GAC). CB-839 had antiproliferative activity in a triple-negative breast cancer (...

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Carfilzomib: a next-generation proteasome inhibitor for multiple myeloma treatment.

Although the incidence of multiple myeloma (MM) is increasing, the median overall survival and the number of agents in the pipeline for treating MM also are increasing. Response rates higher than 80% are not uncommon in the frontline setting when the novel agents thalidomide, lenalidomide, and bortezomib are used in combination. Response rates and survival also have improved in disease that has...

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Carfilzomib: a novel agent for multiple myeloma.

OBJECTIVES Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients. KEY FINDINGS Carfilzomib is a selective proteasome inhibitor that differs struc...

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The NF-kappaB inhibitor LC-1 has single agent activity in multiple myeloma cells and synergizes with bortezomib.

Multiple myeloma remains incurable with conventional therapeutics. Thus, new treatments for this condition are clearly required. In this study we evaluated the novel NF-kappaB inhibitor LC-1 in multiple myeloma cell lines and plasma cells derived from multiple myeloma patients. LC-1 was cytotoxic to multiple myeloma cell lines H929, U266, and JJN3, and induced apoptosis in a dose-dependent mann...

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ژورنال

عنوان ژورنال: Oncotarget

سال: 2017

ISSN: 1949-2553

DOI: 10.18632/oncotarget.16262