title: Update on Janus kinase antagonists in inflammatory bowel disease.
abstract: Janus kinase (JAK) inhibitors have emerged as a novel orally administered small-molecule therapy for the treatment of ulcerative colitis and possibly Crohn disease. These molecules are designed to selectively target the activity of specific JAKs and to offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Digestive Diseases Research Development Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Brigid S
authors.initials: BS
authors.lastname: Boland
authors.affiliation: Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Digestive Diseases Research Development Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Digestive Diseases Research Development Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: changj@ucsd.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
mesh_terms: D000818:Animals; D050171:Dyslipidemias / Q000139:chemically induced; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency; D009894:Opportunistic Infections / Q000139:chemically induced; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases
keywords: Crohn disease; Inflammatory bowel disease; Janus kinase inhibitors; Small-molecule therapy; Tofacitinib; Ulcerative colitis
references.citation: Lancet. 2012 Nov 3;380(9853):1590-605
references.pmid: 22914295
references.citation: N Engl J Med. 2009 Nov 19;361(21):2066-78
references.pmid: 19923578
references.citation: Science. 1994 Jun 3;264(5164):1415-21
references.pmid: 8197455
references.citation: Ann Rheum Dis. 2014 Jan;73(1):124-31
references.pmid: 23482473
references.citation: J Med Chem. 2010 Dec 23;53(24):8468-84
references.pmid: 21105711
references.citation: Blood. 2012 Aug 9;120(6):1202-9
references.pmid: 22718840
references.citation: Immunol Rev. 2009 Mar;228(1):273-87
references.pmid: 19290934
references.citation: Nature. 2012 Nov 1;491(7422):119-24
references.pmid: 23128233
references.citation: N Engl J Med. 2012 Aug 9;367(6):508-19
references.pmid: 22873531
references.citation: Gastroenterology. 1990 Apr;98(4):811-8
references.pmid: 2179031
references.citation: Oncogene. 1992 Jul;7(7):1347-53
references.pmid: 1620548
references.citation: Immunity. 2008 Jun;28(6):763-73
references.pmid: 18549798
references.citation: N Engl J Med. 2012 Aug 9;367(6):495-507
references.pmid: 22873530
references.citation: N Engl J Med. 2010 Sep 16;363(12):1117-27
references.pmid: 20843246
references.citation: Science. 1997 Sep 12;277(5332):1630-5
references.pmid: 9287210
references.citation: Curr Opin Pharmacol. 2012 Aug;12(4):464-70
references.pmid: 22819198
references.citation: N Engl J Med. 2013 Jan 10;368(2):161-70
references.pmid: 23301733
references.citation: Clin Rheumatol. 2013 Oct;32(10):1415-24
references.pmid: 23877486
references.citation: Immunity. 2012 Apr 20;36(4):515-28
references.pmid: 22520845
references.citation: N Engl J Med. 2011 Nov 3;365(18):1713-25
references.pmid: 22047562
references.citation: Nature. 2007 Jul 26;448(7152):427-34
references.pmid: 17653185
references.citation: N Engl J Med. 2011 Oct 27;365(17):1612-23
references.pmid: 22029983
references.citation: Science. 2003 Oct 31;302(5646):875-8
references.pmid: 14593182
references.citation: J Pediatr. 2012 Jun;160(6):1055-7
references.pmid: 22402565
references.citation: Gastroenterology. 2006 Feb;130(2):323-33; quiz 591
references.pmid: 16472588
references.citation: Nat Biotechnol. 2008 Jan;26(1):127-32
references.pmid: 18183025
references.citation: Arthritis Rheumatol. 2015 Feb;67(2):334-43
references.pmid: 25385260
references.citation: Arthritis Rheum. 2006 Sep;54(9):2817-29
references.pmid: 16947782
references.citation: J Biol Chem. 2002 Dec 6;277(49):47954-63
references.pmid: 12351625
references.citation: J Immunol. 2011 Apr 1;186(7):4234-43
references.pmid: 21383241
references.citation: Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii111-5
references.pmid: 23532440
references.citation: N Engl J Med. 1997 Oct 9;337(15):1029-35
references.pmid: 9321530
references.citation: J Allergy Clin Immunol. 2010 Apr;125(4):790-7
references.pmid: 20371393
references.citation: Nat Rev Immunol. 2003 Nov;3(11):900-11
references.pmid: 14668806
references.citation: Ann Intern Med. 2013 Aug 20;159(4):253-61
references.pmid: 24026258
references.citation: Clin Gastroenterol Hepatol. 2011 Aug;9(8):670-678.e3
references.pmid: 21642014
references.citation: Eur J Immunol. 2000 Mar;30(3):732-7
references.pmid: 10741387
references.citation: J Inflamm (Lond). 2010 Aug 11;7:41
references.pmid: 20701804
references.citation: Gut. 1994 Feb;35(2):231-5
references.pmid: 7508411
references.citation: Curr Opin Immunol. 2001 Jun;13(3):363-73
references.pmid: 11406370
references.citation: Aliment Pharmacol Ther. 2013 Apr;37(8):786-94
references.pmid: 23432394
references.citation: Clin Gastroenterol Hepatol. 2014 Sep;12(9):1485-93.e2
references.pmid: 24480677
references.citation: Biochem J. 2003 Mar 1;370(Pt 2):391-6
references.pmid: 12521379
references.citation: N Engl J Med. 2012 Aug 16;367(7):616-24
references.pmid: 22894574