title: Pharmacology of Modulators of Alternative Splicing.
abstract: More than 95% of genes in the human genome are alternatively spliced to form multiple transcripts, often encoding proteins with differing or opposing function. The control of alternative splicing is now being elucidated, and with this comes the opportunity to develop modulators of alternative splicing that can control cellular function. A number of approaches have been taken to develop compounds that can experimentally, and sometimes clinically, affect splicing control, resulting in potential novel therapeutics. Here we develop the concepts that targeting alternative splicing can result in relatively specific pathway inhibitors/activators that result in dampening down of physiologic or pathologic processes, from changes in muscle physiology to altering angiogenesis or pain. The targets and pharmacology of some of the current inhibitors/activators of alternative splicing are demonstrated and future directions discussed.
authors.affiliation: Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (D.O.B.); School of Chemistry, UNSW Australia, Sydney, Australia (J.C.M.); School of Physiology, Pharmacology and Neurosciences, School of Clinical Sciences/Bristol Renal, University of Bristol, Bristol, United Kingdom (S.O.); and School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (L.F.D.) David.Bates@nottingham.ac.uk.
authors.forename: David O
authors.initials: DO
authors.lastname: Bates
authors.affiliation: Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (D.O.B.); School of Chemistry, UNSW Australia, Sydney, Australia (J.C.M.); School of Physiology, Pharmacology and Neurosciences, School of Clinical Sciences/Bristol Renal, University of Bristol, Bristol, United Kingdom (S.O.); and School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (L.F.D.).
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (D.O.B.); School of Chemistry, UNSW Australia, Sydney, Australia (J.C.M.); School of Physiology, Pharmacology and Neurosciences, School of Clinical Sciences/Bristol Renal, University of Bristol, Bristol, United Kingdom (S.O.); and School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (L.F.D.).
authors.forename: Sebastian
authors.initials: S
authors.lastname: Oltean
authors.affiliation: Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (D.O.B.); School of Chemistry, UNSW Australia, Sydney, Australia (J.C.M.); School of Physiology, Pharmacology and Neurosciences, School of Clinical Sciences/Bristol Renal, University of Bristol, Bristol, United Kingdom (S.O.); and School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (L.F.D.).
authors.forename: Lucy F
authors.initials: LF
authors.lastname: Donaldson
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects*; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D012313:RNA