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Small-molecule inhibitors of the Myc oncoprotein
#MMPMID24657798
Fletcher S
; Prochownik EV
Biochim Biophys Acta
2015[May]; 1849
(5
): 525-43
PMID24657798
show ga
The c-Myc (Myc) oncoprotein is among the most attractive of cancer targets given
that it is de-regulated in the majority of tumors and that its inhibition
profoundly affects their growth and/or survival. However, its role as a
seldom-mutated transcription factor, its lack of enzymatic activity for which
suitable pharmaceutical inhibitors could be crafted and its expression by normal
cells have largely been responsible for its being viewed as "undruggable". Work
over the past several years, however, has begun to reverse this idea by allowing
us to view Myc within the larger context of global gene regulatory control. Thus,
Myc and its obligate heterodimeric partner, Max, are integral to the coordinated
recruitment and post-translational modification of components of the core
transcriptional machinery. Moreover, Myc over-expression re-programs numerous
critical cellular functions and alters the cell's susceptibility to their
inhibition. This new knowledge has therefore served as a framework upon which to
develop new pharmaceutical approaches. These include the continuing development
of small molecules which act directly to inhibit the critical Myc-Max
interaction, those which act indirectly to prevent Myc-directed
post-translational modifications necessary to initiate productive transcription
and those which inhibit vital pathways upon which the Myc-transformed cell is
particularly reliant. This article is part of a Special Issue entitled: Myc
proteins in cell biology and pathology.
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