title: Bromodomain inhibitors and cancer therapy: From structures to applications.
abstract: Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are "writers," "erasers," or "readers" of histone modification marks are common. Bromodomains are "readers" that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains. In recent years, there has been increasing interest in developing small molecules that can target specific bromodomains. First, this has helped clarify biological functions of bromodomain-containing proteins. Secondly, it opens a new front for combatting cancer. In this review we will describe the structures and mechanisms associated with Bromodomain and Extra-Terminal motif (BET) inhibitors and non-BET inhibitors, their current status of development, and their promising role as anti-cancer agents.
authors.affiliation: a Cancer Epigenetics and Biology Program (PEBC) , Bellvitge Biomedical Research Institute (IDIBELL) , Barcelona , Catalonia , Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pérez-Salvia
authors.affiliation: a Cancer Epigenetics and Biology Program (PEBC) , Bellvitge Biomedical Research Institute (IDIBELL) , Barcelona , Catalonia , Spain.|b Department of Physiological Sciences II, School of Medicine , University of Barcelona , Barcelona , Catalonia , Spain.|c Institució Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona , Catalonia , Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002843:Chromatin / Q000187:drug effects; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D042421:Histone Code / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D000072417:Protein Domains / Q000187:drug effects; D000092468:Bromodomain Containing Proteins
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D008239:Lysine; D009687:Nuclear Proteins; C402649:BRD1 protein, human; D000092468:Bromodomain Containing Proteins
keywords: Acetylation; bromodomain and extra-terminal motif inhibitors; cancer; epigenetics; histone marks