Histone deacetylase (HDAC) inhibitors are emerging as a new class of potential anticancer agents for the treatment of solid and hematological malignancies. HDAC inhibition causes acetylated nuclear histones to accumulate in both tumor and normal tissues, providing a surrogate marker for the biological activity of HDAC inhibitors in vivo. The effects of HDAC inhibitors on gene expression are highly selective, leading to transcriptional activation of certain genes such as the cyclin-dependent kinase inhibitor but repression of others. HDAC inhibition not only results in acetylation of histones but also transcription factors such as p53, GATA-1 and estrogen receptor-alpha.

HDAC inhibitors are potent antiproliferative agents with relatively little effect on normal tissues. The first generation of pan-HDAC inhibitor produced clinical benefit and the first representative of this class is already marketed for cutaneous T-cell lymphoma. The second generation inhibitors are rationally designed with improved specificity and are currently in broad clinical evaluation for a number of different cancer indications, alone and in combination.

Apart from oncology, HDAC inhibitors are also being evaluated in other indications, such as Huntington’s disease or Friedreich’s ataxia because transcriptional dysregulation has been shown to be a major pathology in Huntington's Disease. There are CNS-penetrant, orally bioavailable HDAC inhibitors which are being pursued for use as a cognition enhancing agent in neurodegenerative diseases such as Alzheimer’s disease. Other indications under evaluation are fungal infections, psoriasis and inflammatory diseases.

Related report:
Competitor Analysis: HDAC Inhibitors

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