title: LSD1: biologic roles and therapeutic targeting.
abstract: LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: Alba
authors.initials: A
authors.lastname: Maiques-Diaz
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: Tim Cp
authors.initials: TC
authors.lastname: Somervaille
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: GSK2879552; LSD1; ORY1001; acute myeloid leukemia; histone demethylase; small-cell lung cancer