HDACiDB: a database for histone deacetylase inhibitors

Abstract

An histone deacetylase (HDAC) inhibitor database (HDACiDB) was constructed to enable rapid access to data relevant to the development of epigenetic modulators (HDAC inhibitors [HDACi]), helping bring precision cancer medicine a step closer. Thousands of HDACi targeting HDACs are in various stages of development and are being tested in clinical trials as monotherapy and in combination with other cancer agents. Despite the abundance of HDACi, information resources are limited. Tools for in silico experiments on specific HDACi prediction, for designing and analyzing the generated data, as well as custom-made specific tools and interactive databases, are needed. We have developed an HDACiDB that is a composite collection of HDACi and currently comprises 1,445 chemical compounds, including 419 natural and 1,026 synthetic ones having the potential to inhibit histone deacetylation. Most importantly, it will allow application of Lipinski’s rule of five drug-likeness and other physicochemical property-based screening of the inhibitors. It also provides easy access to information on their source of origin, molecular properties, drug likeness, as well as bioavailability with relevant references cited. Being the first comprehensive database on HDACi that contains all known natural and synthetic HDACi, the HDACiDB may help to improve our knowledge concerning the mechanisms of actions of available HDACi and enable us to selectively target individual HDAC isoforms and establish a new paradigm for intelligent epigenetic cancer drug design. The database is freely available on the http://hdacidb.bioinfo.au-kbc.org.in/hdacidb/website.

Lysine Deacetylases Exhibit Distinct Changes in Activity Profiles Due to Fluorophore Conjugation of Substrates

“…12-15 Properly regulated acetylation and deacetylation have been linked to many biological processes, while aberrant KDAC activity has also been linked to numerous diseases. 4,5 Based on the therapeutic potential of regulating KDACs in vivo , research efforts are focused on identifying molecules that inhibit or activate these enzymes, 5,16-18 as well as identifying substrates of specific KDACs. 19-23 …”

Current situation and future usage of anticancer drug databases

“…A tremendous number of HDACis have been developed in various stages for clinical trials as monotherapy or combined with other anticancer drugs. histone deacetylase inhibitor database (HDACiDB) [35], the first comprehensive database on HDACi, has been constructed to facilitate the rapid access to the information of HDACis development. Up to now, HDACiDB is comprised of 1445 inhibitors including 419 natural compounds and 1026 synthetic compounds.…”

Purification of metal-dependent lysine deacetylases with consistently high activity

“…In addition, KDAC8 is inhibited by excess zinc which binds to a second site on the enzyme [3]. Over 1000 inhibitors for KDACs have been identified, and several are in clinical trials or have already been approved for therapeutic use [11,12]. Despite high interest in understanding KDAC function, relatively few substrates (i.e.…”