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Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia

Jenkins, Christopher, Hewamana, Saman, Krige, David, Pepper, Christopher John and Burnett, Alan Kenneth 2011. Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia. Leukemia Research 35 (5) , pp. 677-681. 10.1016/j.leukres.2010.10.030

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Abstract

Aminopeptidase enzyme inhibition is thought to deplete the free intracellular amino acids needed by malignant cells for growth and development, resulting in profound anti-proliferative and apoptotic effects. In this study, we investigated the effects of the metalloenzyme-inhibitor CHR-2797 (tosedostat), in primary acutemyeloidleukemia (AML) cells. CHR-2797 demonstrated marked in vitro cytotoxicity in AML samples and strong synergy with Cytarabine (Ara-C), but significantly less cytotoxicity to normal marrow progenitors. Furthermore mechanistic investigations revealed that CHR-2797 inhibited the intrinsic nuclear, cytoplasmic and cell surface aminopeptidase function of AML blasts in a dose-dependent manner, demonstrating a promising novel approach for AML therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Aminopeptidases; Metalloenzymes; CHR-2797; Tosedostat; Acutemyeloidleukemia; CD13; Molecular therapeutics
Publisher: Elsevier
ISSN: 0145-2126
Last Modified: 25 Jun 2017 03:14
URI: http://orca-mwe.cf.ac.uk/id/eprint/25302

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