2 research outputs found
Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101
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