Bromodomain and extra-terminal (BET) inhibitors are small molecule inhibitors including bromodomain 2 (BRD2), bromodomain 3 (BRD3), bromodomain 4 (BRD4) and bromodomain testis (BRDT), which have anti-proliferating properties. These targets of inhibitors are supposed to bind with myc gene, which is a most desired target for cancer therapeutics. BET inhibitors are first-in-class targeted therapies that directly target bromodomain proteins to deliver a new therapeutic prospect as inhibition of epigenetic regulators.
BET inhibitor constitutes that class of drugs that prevents interactions between BET proteins, and transcription factors and acetylated histone. This results in immunosuppressive and anti-cancer properties of BET inhibitor. BET inhibitors when administered, bind to acetylated lysine motifs, thus, preventing interaction between acetylated lysine and BET proteins. This disrupts the gene expression and chromatin remodeling. Inhibition of certain growth promoting genes results in reducing tumor cell growth. BET proteins play an important role in cell growth and development as transcriptional regulators. Inhibition of BET proteins offered a new therapeutic approach for the treatment of cancer, cardiovascular diseases and other diseases.
The discovery of BET proteins shows that they play a crucial role in transcriptional activation, and thus, have oncogenic potential. This has resulted in the development of several small molecule BET inhibitors. Preclinical studies have shown promising results for many indications, both in in-vitro and in-vivo studies. There are many early phase clinical trials for these inhibitors that are presently testing the efficacy of BET inhibitors.
The BET inhibitors pipeline is very strong, with approximately 38 drug candidates in different stages of development.
Some of the key players developing BET inhibitors are Resverlogix Corp., GlaxoSmithKline plc, Bristol-Myers Squibb Company and others.
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