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Pharmaceutical Technology

Pharmaceutical Technology-03-02-2008
Volume32
Issue 3

Coming Down the Pike: HDAC inhibitors

New research and ideas for March 2008

Finally, after years of focusing almost exclusively on kinases as targets for anticancer therapies, a new class of compound makes the jump from research laboratory to clinical development. The new kid on the block: Histone deactelyase inhibitors (HDAC inhibitors). These compounds prevent the expression of cancer-inducing genes by maintaining them in a suppressed state. Essentially, these new potential anticancer therapies take advantage of an epigenetic mechanism of controlling gene expression. That is, certain chemical modifications can suppress the expression of genes without altering the intrinsic sequence of nucleotides in the DNA code—hence the notion of epigenetic modification. Instead, these modifications—chiefly methylation or acetylation—somehow alter the structure of the chromatin in which the gene lies in such a way that a particular stretch of chromatin is tightly coiled and resistant to unwinding by transcription factors that might otherwise stimulate gene expression. If the suppressed gene contributes to carcinogenesis, then inhibiting its expression should inhibit its ability to cause cancer. HDAC inhibitors function by preventing the removal of suppressive acetyl groups from histone proteins on the chromatin. Several large pharma and biotech companies are developing HDAC inhibitors as anticancer therapies, some of which are in clinical trials.

Source: M. Paris et. al., "Histone Deacetylase Inhibitors: From Bench to Clinic," J. Med. Chem., ASAP Article, 10.1021/jm7011408, (Feb. 5, 2008), available at pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/asap/abs/jm7011408.html, accessed Feb. 14, 2008.

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