Future Science - Future Medicinal Chemistry - 4(4):505 - Summary
Review
Abstract
Targeted cancer therapy: giving histone deacetylase inhibitors
"Histone
deacetylase inhibitors (HDACis) have now emerged as a powerful new
class of small-molecule therapeutics acting through the regulation of
the acetylation states of histone proteins (a form of epigenetic
modulation) and other non-histone protein targets. Over 490 clinical
trials have been initiated in the last 10 years, culminating in the
approval of two structurally distinct HDACis – SAHA (vorinostat,
Zolinza™) and FK228 (romidepsin, Istodax™).
However, the current HDACis
have serious limitations, including ineffectively low concentrations in
solid tumors and cardiac toxicity, which is hindering their progress in
the clinic. Herein, we review the primary paradigms being pursued to
overcome these hindrances, including HDAC isoform selectivity, localized
administration, and targeting cap groups to achieve selective tissue
and cell type distribution."