Epigenetic regulators fall into three main categories: writers, erasers, and readers. Writers modify histones by adding chemical groups that result in acetylation, phosphorylation, methylation, or other modification types (KnoWhereBio’s Critical Cysteine Modification: Redox Modification), while erasers remove these groups.
The critical task of recognizing these modifications falls to reader proteins. Together, these regulators control gene transcription by either directly or indirectly altering the chromatin structure. Open chromatin configurations facilitate transcription by permitting access to DNA wrapped around histones, resembling a thread around a spool. Closed configurations limit access which impedes transcription.
BETi department is developing first-in-class drugs against cancer, and inflammatory diseases focusing on Bromodomain and Extra-Terminal domain (BET) protein inhibitors that block the lysine residues of histone tails with BET proteins as the epigenetic reader molecules.
To find potent inhibitory activities against BET proteins, we used various kinds of strategies such as chemical synthesis of natural compounds’ derivatives (80 billion DNA encoded chemical library screening), combinatorial protein library screening, and computer-aided drug design based on virtual in silico library screening.
We applied the science of redox biochemistry and post-translational modifications for the design of new drugs.