Clinical progress and pharmacology of small molecule bromodomain inhibitors

• Published in: Current opinion in chemical biology 2016-08, Vol.33, p.58-66
• Main Authors: Theodoulou, Natalie H, Tomkinson, Nicholas CO, Prinjha, Rab K, Humphreys, Philip G
• Format: Article
• Language: English
• Subjects: Clinical Trials as Topic; Drug Discovery; Humans; Models, Molecular; Molecular Probes; Proteins - chemistry; Small Molecule Libraries - chemistry
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2016.05.028

[Display omitted] •Bromodomains are an exciting and important target class for drug discovery.•Multiple small molecule BET bromodomain inhibitors undergoing clinical trials with encouraging emerging data.•High quality chemical probes are an important tool for the target validation of non-BET bromodomains.•Increasing number of non-BET bromodomain chemical probes showing interesting pharmacology. Bromodomains have emerged as an exciting target class for drug discovery over the past decade. Research has primarily focused on the bromodomain and extra terminal (BET) family of bromodomains, which has led to the development of multiple small molecule inhibitors and an increasing number of clinical assets. The excitement centred on the clinical potential of BET inhibition has stimulated intense interest in the broader family and the growing number of non-BET bromodomain chemical probes has facilitated phenotypic investigations, implicating these targets in a variety of disease pathways including cancer, inflammation, embryonic development and neurological disorders.