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ABSTRACT
Introduction: Epigenetic modification has been implicated in a wide range of diseases and the ability to modulate such systems is a lucrative therapeutic strategy in drug discovery.
Areas covered: This article focuses on the concepts and drug discovery aspects of epigenomics. This is achieved by providing a survey of the following concepts: (i) factors influencing epigenetics, (ii) diseases arising from epigenetics, (iii) epigenetic enzymes as druggable targets along with coverage of existing FDA-approved drugs and pharmacological agents, and (iv) drug repurposing/repositioning as a means for rapid discovery of pharmacological agents targeting epigenetics.
Expert opinion: Despite significant interests in targeting epigenetic modifiers as a therapeutic route, certain classes of target proteins are heavily studied while some are less characterized. Thus, such orphan target proteins are not yet druggable with limited report of active modulators. Current research points towards a great future with novel drugs directed to the many complex multifactorial diseases of humans, which are still often poorly understood and difficult to treat.
Article highlights
Epigenetic events act as a mediator between the external/environmental factors (cause) and the manifested genetic landscape regulation (effect). Therefore, lifestyle choices and environmental factors affect gene expression thereby influencing the etiology of various diseases.
In a nutshell, epigenetic events allow a reversible and robust switching on and off of gene expression via the attachment and processing of chemical tags on DNA and histones thereby regulating the euchromatin state that is required for active transcription.
Dysregulation of targets mediating epigenetic events can give rise to pathological deterioration associated with cardiovascular diseases, neurological disorders, metabolic disorders, and cancer development. Epigenomic targets thus represents an attractive avenue for pharmacological intervention by small molecules.
Epigenetic drugs have primarily been studied for their use in treating cancer, however research on their use in Alzheimer’s, Asthma and a myriad of other CNS, CVS, inflammatory/immune diseases is steadily rising.
Great interest has been invested in the discovery of inhibitors or modulators against several key epigenetic drug targets. However, current epigenetic modulators lack isoform selectivity and produce global epigenetic changes. Advances in structural/functional genomics and chemical biology have provided insights into the isoform selectivity requirements and sequence-specific epigenetic chemical probes.
Drug repositioning or drug repurposing represents an interesting route for the rapid discovery of novel drugs targeting the epigenetic machinery and for expanding the therapeutic indication profiles of existing epigenetic drugs.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties