BET inhibitors in cancer therapeutics: a patent review

ABSTRACT

Introduction: Inhibition of Bromodomain and Extra Terminal (BET) proteins is an emerging approach for developing advanced cancer therapeutics. In 2015, at least thirty patents have been published for developing cancer chemotherapeutics by targeting BET. Currently there are seven small molecule BET inhibitors in various stages of clinical trials for the development of anti-cancer drugs.

Areas covered: Important patents focusing on development of BET inhibitors as potential cancer therapeutics published in 2015 have been covered. The reports are presented together with a review of the related structural chemical space. This review mainly focuses on the therapeutic applications, chemical class and structural modifications along with the molecules currently in clinical trials.

Expert opinion: BET sub-family proteins are one of the emerging targets to develop anti-cancer agents. Although many research groups have demonstrated the rationality of BET inhibition to combat cancer, a detailed molecular study needs to be performed to investigate the affected biological pathways. Selectivity among BET proteins should be kept in mind while developing BET inhibitors. In-silico molecular modelling studies can also provide valuable information for designing selective BET inhibitors towards anti-cancer drug discovery and development.

KEYWORDS:

• Bromodomain
• Bromodomain and Extra Terminal Proteins
• BET
• anti-cancer

Article highlights

• Inhibition of BET bromodomain proteins is an emerging and widely explored epigenetic approach for the development of novel and potential anticancer therapeutics.

• The structural diversity of the novel and emerging bromodomain inhibitors is evident from the patents published in 2015 – diazepines, pyrroles, pyrazoles, isoxazoles, quinolines, quinazolines are some of the chemical scaffolds that have been explored as potential BET inhibitors for anticancer drug discovery.

• Synergistic action of bromodomain inhibitors with kinase inhibitors, PI3K inhibitors, HDAC inhibitors, and DNA methylation inhibitors can be used as an effective therapeutic strategy to treat cancer.

• Successful clinical trials of JQ1, I-BET 762, I-BET 151, OTX-015, TEN-010, CPI-0610, and BAY 1,238,097 will decide the future scope and prospects of BET inhibitors for anticancer drug discovery.

• The patented bromodomain inhibitors are therapeutically effective against NMC, AML, acute lymphoblastic leukemia (ALL), breast cancer, ovarian cancer, and also against various other types of cancer.

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Declaration of interest

This work has been supported by CSIR-Indian Institute of Chemical Technology. The authors have no other 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 apart from those disclosed.