Histone Deacetylases (HDACs) are a super family of enzymes catalyzing removal of acetyl functional groups from lysine residues of histone proteins. HDACs help in wrapping of histone over the deoxyribonucleic acid (DNA). Thus play an imperative role in gene expression and cell functioning. The mammalian HDAC family comprises 11 enzymes categorized into four classes – Class I, Class II, Class III and Class IV. Class I and II HDACs, in addition to deacetylating histones for the inhibition of transcription also deacetylate lysine residues of other regulatory proteins to modulate their functions. Class III HDACs, also known as sirtuins, are principally involved in metabolic processes and aging and also regulate other cellular functions. Class IV contains only HDAC11. Mounting evidence indicates aberrant HDAC activity is implicated in various oncologic and non-oncologic diseases. Thus development of HDAC inhibitors, targeted drug molecules which inhibit activity of HDACs, garners a lot of interest from academic researchers and bio-pharmaceutical firms.
Some of the key HDAC inhibitors currently available in market are Zolinza (vorinostat), Epidaza (chidamide), and Beleodaq (belinostat) for the treatment of ovarian cancer, acute myelogenous leukemia, non small cell lung cancer, Non-Hodgkin’s lymphoma, hematological malignancies, multiple myeloma, renal cell carcinoma, melanoma, pancreatic cancer, breast cancer, and graft versus host disease. HDAC pipeline too is quite robust with more than 40 molecules in various stages of clinical development. Few of the key pipeline HDAC inhibitors include entinostat, pracinostat (SB939), abexinostat, CHR-5154, CKD-581, RG2833, MPT0E028, and CS3158. In pipeline analysis, these are analyzed on the basis of route of administration (ROA) and type of molecule. The pipeline is also assessed based on monotherapy and combination therapy, and different clinical phases including Phase III, Phase II, Phase I and Pre-Clinical stage.
Few of the companies which are involved in the development of HDAC inhibitor are Chipscreen, Celgene, Syndax, AbbVie, Merck, Novartis, Celldex, GSK, Chroma, and Onxeo. There are numerous factors of HDAC inhibitor which would help in the growth of market and also continue the impact of these inhibitors in the market.
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