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Protease Inhibitors

Transcription in eukaryotic cells depends on how DNA is packaged. Under resting conditions, DNA is tightly compacted into a protein-DNA complex called chromatin to prevent access by transcription factors. The fundamental subunit of chromatin, the nucleosome, is composed of an octamer of four core histones: a H3-H4 tetramer and two H2A-H2B dimers, wound around by 146 bp of DNA. Histone deacetylases (also known as HDACs) are a group of enzymes that remove acetyl groups (O=C-CH3) from a ε-N-acetyl lysine amino acid on a histone protein, so that the histones can wrap more tightly around the DNA during chromatin packing. There are 18 human HDACs grouped into four classes based on their function and their domain structure: Class I includes HDAC1, 2, 3, and 8; Class II includes HDAC4, 5, 6, 7, 9 and 10; Class III includes Sirtuins in mammals and Class IV includes HDAC 11. Classes I and II can be inhibited by Trichostatin A (TSA) but Class III is NAD+ dependent and cannot be inhibited by TSA.

Canonically, HDAC inhibitors (HDIs) have been used as mood stabilizers and anti-epileptic drugs (eg. Valproic acid). Currently Valproic acid is in clinical trial for its killing potency against latent pools of HIV. HDIs are also an important point of focus for neurodegenerative disease research. Since acetylation is key to regulating gene expression patterns in vivo, the study of HDACs in relation to the aberrant gene expression observed in cancer is only logical. Naturally, significant research efforts have focused on the potential use of histone deacetylase inhibitors as anticancer agents. HDAC inhibitors modify the acetylation state of a many cellular proteins (e.g. NF-KB, p53 etc.) in addition to histones thus resulting in global antitumor effects in various cell types. Vorinostat (SAHA) has recently been approved for treatment of cutaneous T cell lymphoma. Additionally, HDIs are also being studied to act as chemosensitizers for chemotherapy. BioVision's product list includes many of the above mentioned HDAC inhibitors and more.


Protease Inhibitors List

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