Post-translational modifications, such as acetylation or phosphorylation, play a crucial role in the regulation of gene transcription in eukaryotes. Different subtypes of histone acetyltransferases (HATs) catalyze the acetylation of histones on specific lysine residues.
A potential involvement of HATs in the pathology of cancer, asthma, COPD and viral infection has been described.
The role of the HATs p300, CBP, PCAF and GCN5 in different diseases has evoked great interest in the development of small-molecule inhibitors of these enzymes as potential drugs.
Histone Acetyltransferase Targeted Library (814 compounds in total)
offered by OTAVAchemicals has been designed to select compounds towards PCAF, p300, GCN5, and MOZ histone acetyltransferases. Receptor-based virtual screen of Drug-like Green Collection
against these four HATs was validated with a reference set
of known histone acetyltransferase inhibitors obtained from ChemblDB.
Final selection of compounds has been made with inspection of active site’s critical structural determinants for ligand binding, docking score cut-off filtering, intermolecular hydrogen bonds with key active site’s residues taken from literature reviews and exclusion of predicted cross-binders. The overal procedure included initial vitrtual screening followed by precise flexible docking with extended intermolecular hydrogen bond filtering applied during the selection.
The library consists of the following compound sets:
Histone Acetyltransferase PCAF inhibitors - 75 compounds
Histone Acetyltransferase p300 inhibitors - 358 compounds
Histone Acetyltransferase GCN5 inhibitors - 180 compounds
Histone Acetyltransferase MOZ inhibitors - 201 compounds
This library comprises drug-like compounds only and provides an excellent basis for epigenetic drug discovery.
Examples of compounds from OTAVAchemicals Histone Acetyltransferase Target-Focused Library docked into HAT's active site
All the compounds are in stock, cherry-picking is available.
The library (DB, SD, XLS, PDF format) as well as the price-list is available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.
Dekker FJ, Haisma HJ. Histone acetyl transferases as emerging drug targets. Drug Discov Today. 2009 (19-20):942-8