title: Small-molecule control of cytokine function: new opportunities for treating immune disorders.
abstract: Manipulating cytokine function with protein-based drugs has proven effective for treating a wide variety of autoimmune and autoinflammatory disorders. However, the limited ability of protein-based drugs to modulate intracellular targets, including many implicated by studies of the genetics and physiology of these diseases, and to coordinately neutralize redundant inflammatory cytokines, suggests an important and complementary role for small molecules in immunomodulatory drug development. The recent clinical approval of Janus kinase and phosphodiesterase inhibitors, along with emerging evidence from other compound classes, firmly establish small molecules as effective tools for modulating therapeutically relevant proteins that give rise to aberrant cytokine signaling or mediate its downstream consequences.
authors.affiliation: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Sundberg
authors.affiliation: Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.affiliation: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA. Electronic address: ashamji@broadinstitute.org.
authors.forename: Alykhan F
authors.initials: AF
authors.lastname: Shamji
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D055808:Drug Discovery; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D054852:Small Molecule Libraries