Year: 2014
Type: article
Abstract: The bromodomain and extraterminal domain (BET)-containing proteins are a class of epigenetic regulators known as “chromatin readers,” which bind to acetylated lysines on histones, recruit transcription factors and chromatin-modifying enzymes, and can function as co-activators or co-repressors of gene transcription depending on the context.1,2 BRD4 (bromodomain containing 4) is a conserved member of the BET family protein that includes other subfamily members such as BRD2, BRD3, and testis-specific BRDT. Studies with the small molecules, JQ1 and I-BET762, were the first to indicate the druggability of the BET bromodomain family.1,2 In addition to the NUT–BRD3/4 fusion in NUT midline carcinomas, MLL fusions in leukemias and MYC overexpression in variety of cancers have been suggested as targets of BET bromodomain inhibitors.1-3 Importantly, JQ1 has exhibited little or no toxicity in mice treated with high levels (50 mg/kg daily) over a month. While JQ1 itself is not a clinical lead compound, trials with BET inhibitors GSK525762 (GlaxoSmithKline), CPI-0610 (Constellation Pharmaceuticals), TEN-010 (Tensha Therapeutics), and OTX-015 (Oncoethix) have been initiated for a variety of malignancies, and several other BET inhibitors are in pre-clinical development.4 Due to their favorable side-effect profiles, BET inhibition has even been contemplated in non-disease indications such as male contraception.5
Source: Cell Cycle
DOI: 10.4161/cc.29459
Authors: Irfan A Asangani, Arul M. Chinnaiyan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funder: Howard Hughes Medical Institute
OpenAlex ID: W2011853700