eprintid: 20651 rev_number: 20 userid: 1419 dir: disk0/00/02/06/51 datestamp: 2014-07-01 17:20:22 lastmod: 2019-02-04 23:55:04 status_changed: 2014-07-01 17:20:22 type: article metadata_visibility: show item_issues_count: 0 eprint_status: archive creators_name: Braunstein, MJ creators_name: Scott, SS creators_name: Scott, CM creators_name: Behrman, S creators_name: Walter, P creators_name: Wipf, P creators_name: Coplan, JD creators_name: Chrico, W creators_name: Joseph, D creators_name: Brodsky, JL creators_name: Batuman, O creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: pwipf@pitt.edu creators_email: creators_email: creators_email: creators_email: jbrodsky@pitt.edu creators_email: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: PWIPF creators_id: creators_id: creators_id: creators_id: JBRODSKY creators_id: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: 0000-0002-6984-8486 creators_orcid: title: Antimyeloma effects of the heat shock protein 70 molecular chaperone inhibitor MAL3-101 ispublished: pub divisions: sch_as_chemistry full_text_status: public 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. date: 2011-11-24 date_type: published publication: Journal of Oncology refereed: TRUE issn: 1687-8450 id_number: 10.1155/2011/232037 other_id: NLM PMC3184436 pmcid: PMC3184436 pmid: 21977030 citation: 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 document_url: http://d-scholarship-dev.library.pitt.edu/20651/1/licence.txt