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Antimyeloma effects of the heat shock protein 70 molecular chaperone inhibitor MAL3-101

Braunstein, MJ and Scott, SS and Scott, CM and Behrman, S and Walter, P and Wipf, P and Coplan, JD and Chrico, W and Joseph, D and Brodsky, JL and Batuman, O (2011) Antimyeloma effects of the heat shock protein 70 molecular chaperone inhibitor MAL3-101. Journal of Oncology. ISSN 1687-8450

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Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. A rational approach to this compelling challenge is to develop new drugs that act synergistically with existing effective agents. This approach will reduce drug concentrations, avoid treatment resistance, and also improve treatment effectiveness by targeting new and nonredundant pathways in MM. Toward this goal, we examined the antimyeloma effects of MAL3-101, a member of a new class of non-ATP-site inhibitors of the heat shock protein (Hsp) 70 molecular chaperone. We discovered that MAL3-101 exhibited antimyeloma effects on MM cell lines in vitro and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients. In combination with a proteasome inhibitor, MAL3-101 significantly potentiated the in vitro and in vivo antimyeloma effects. These data support a preclinical rationale for small molecule inhibition of Hsp70 function, either alone or in combination with other agents, as an effective therapeutic strategy for MM. Copyright © 2011 Marc J. Braunstein et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Braunstein, MJ
Scott, SS
Scott, CM
Behrman, S
Walter, P
Wipf, Ppwipf@pitt.eduPWIPF
Coplan, JD
Chrico, W
Joseph, D
Brodsky, JLjbrodsky@pitt.eduJBRODSKY0000-0002-6984-8486
Batuman, O
Date: 24 November 2011
Date Type: Publication
Journal or Publication Title: Journal of Oncology
DOI or Unique Handle: 10.1155/2011/232037
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1687-8450
Other ID: NLM PMC3184436
PubMed Central ID: PMC3184436
PubMed ID: 21977030
Date Deposited: 01 Jul 2014 17:20
Last Modified: 26 Sep 2022 16:36
URI: http://d-scholarship.pitt.edu/id/eprint/20651

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