{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:54:29Z","timestamp":1793332469454,"version":"4.5.0"},"reference-count":97,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"DOE Office of Biological and Environmental Research"},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["P41GM103393"],"award-info":[{"award-number":["P41GM103393"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"crossref","award":["P41RR001209"],"award-info":[{"award-number":["P41RR001209"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2013,9]]},"DOI":"10.1016\/j.ejmech.2013.03.070","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T21:30:10Z","timestamp":1368567010000},"page":"175-187","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":111,"special_numbering":"C","title":["Lead identification of novel and selective TYK2 inhibitors"],"prefix":"10.1016","volume":"67","author":[{"given":"Jun","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie","family":"Tsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Van Abbema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Beresini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Berezhkovskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade S.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Driscoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Eigenbrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Ghilardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gibbons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Halladay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan Bir","family":"Kohli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya","family":"Liimatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Mantik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapil","family":"Menghrajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Sambrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Shia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ultsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawren C.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Magnuson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2013.03.070_bib1a","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-065X.2008.00754.x","article-title":"Janus kinases in immune cell signaling","volume":"228","author":"Ghoreschi","year":"2009","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib1b","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.16.1.293","article-title":"Jaks and STATs: biological implications","volume":"16","author":"Leonard","year":"1998","journal-title":"Annual Review of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib1c","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0952-7915(98)80165-9","article-title":"Jak\/STAT signaling by cytokines","volume":"10","author":"Liu","year":"1998","journal-title":"Current Opinion in Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev.iy.13.040195.002101","article-title":"Signaling through the hematopoietic cytokine receptors","volume":"13","author":"Ihle","year":"1995","journal-title":"Annual Review of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib3a","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1074-7613(00)00054-6","article-title":"Partial impairment of cytokine responses in Tyk2-deficeint mice","volume":"13","author":"Karaghiosoff","year":"2000","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib3b","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S1074-7613(00)00055-8","article-title":"Tyk2 plays a restricted role in IFN\u03b1 signaling, although it is required for IL-12-mediated T cell function","volume":"13","author":"Shimoda","year":"2000","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib3c","doi-asserted-by":"crossref","first-page":"11594","DOI":"10.1073\/pnas.1930781100","article-title":"A\u00a0natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q\/J mice to infection and autoimmunity","volume":"100","author":"Shaw","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.ejmech.2013.03.070_bib4","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.immuni.2006.09.009","article-title":"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity","volume":"25","author":"Minegishi","year":"2006","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5a","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-381300-8.00005-8","article-title":"The many face-lifts of CD4 T helper cells","volume":"107","author":"Mucida","year":"2010","journal-title":"Advances Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5b","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev.immunol.16.1.495","article-title":"The interleukin-12\/interleukin-12-receptor system: role in normal and pathologic immune responses","volume":"16","author":"Gately","year":"1998","journal-title":"Annual Review of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5c","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.0105-2896.2004.00211.x","article-title":"Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4","volume":"202","author":"Watford","year":"2004","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5d","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1600-065X.2008.00714.x","article-title":"From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited","volume":"226","author":"Boniface","year":"2008","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5e","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nri1648","article-title":"New IL-2 family members: IL-23 and IL-27, cytokines with divergent functions","volume":"5","author":"Hunter","year":"2005","journal-title":"Nature Reviews Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5f","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.0105-2896.2004.00214.x","article-title":"IL-12 and IL-23: master regulators of innate and adaptive immunity","volume":"202","author":"Langrish","year":"2004","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib5g","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S1074-7613(03)00296-6","article-title":"The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses","volume":"19","author":"Trinchieri","year":"2003","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib6a","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4049\/jimmunol.153.1.128","article-title":"Expression cloning of a human IL-12 receptor component","volume":"153","author":"Chua","year":"1994","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib6b","doi-asserted-by":"crossref","first-page":"14002","DOI":"10.1073\/pnas.93.24.14002","article-title":"A\u00a0functional interleukin 12 receptor complex is composed of two \u03b2-type cytokine receptor subunits","volume":"93","author":"Presky","year":"1996","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.ejmech.2013.03.070_bib7","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.4049\/jimmunol.168.11.5699","article-title":"A\u00a0receptor for the heterodimeric cytokine IL-23 is composed of IL-12\u03b21 and a novel cytokine receptor subunit, IL-23R","volume":"168","author":"Parham","year":"2002","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib8a","doi-asserted-by":"crossref","first-page":"7307","DOI":"10.1073\/pnas.92.16.7307","article-title":"Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes","volume":"92","author":"Bacon","year":"1995","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.ejmech.2013.03.070_bib8b","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1074-7613(00)00070-4","article-title":"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12","volume":"13","author":"Oppmann","year":"2000","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1089\/jir.2005.25.733","article-title":"STATs: multifaceted regulators of transcription","volume":"23","author":"Brierley","year":"2005","journal-title":"Journal of Interferon & Cytokine Research"},{"key":"10.1016\/j.ejmech.2013.03.070_bib10a","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/382171a0","article-title":"Requirement for STAT4 in interleukin-12-mediated response of natural killer and T cells","volume":"382","author":"Thierfelder","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2013.03.070_bib10b","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/382174a0","article-title":"Impaired IL-12 responses and enhanced development of Th2 cells in STAT4-deficient mice","volume":"382","author":"Kaplan","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2013.03.070_bib11","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1074\/jbc.M207577200","article-title":"Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17","volume":"278","author":"Aggarwal","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib12a","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJMra0707449","article-title":"Interleukin-17 and type 17 helper cells","volume":"361","author":"Miossec","year":"2009","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.ejmech.2013.03.070_bib12b","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.jaci.2009.04.003","article-title":"Development and function of Th17 cells in health and disease","volume":"123","author":"Louten","year":"2009","journal-title":"Journal of Allergy Clinical Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib12c","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.immuni.2008.03.004","article-title":"The biological functions of T helper 17 cell effector cytokines in inflammation","volume":"28","author":"Ouyang","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib12d","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1600-065X.2008.00705.x","article-title":"The interleukine-23 axis in intestinal inflammation","volume":"226","author":"Ahem","year":"2008","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib13a","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nri2340","article-title":"The genetics and immunopathogenesis of inflammatory bowel disease","volume":"8","author":"Cho","year":"2008","journal-title":"Nature Reviews Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib13b","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng.311","article-title":"Genome-wide scan reveals association of psoriasis with IL-23 and NF-\u03baB pathways","volume":"41","author":"Nair","year":"2009","journal-title":"Nature Genetics"},{"key":"10.1016\/j.ejmech.2013.03.070_bib13c","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1086\/511051","article-title":"A\u00a0large-scale genetic association study confirmed IL12b and leads to the identification of IL23R as psoriasis-risk gene","volume":"80","author":"Cargill","year":"2007","journal-title":"American Journal of Human Genetics"},{"key":"10.1016\/j.ejmech.2013.03.070_bib13d","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00439-007-0397-0","article-title":"Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12b) confer protection against psoriasis","volume":"122","author":"Capon","year":"2007","journal-title":"Human Genetics"},{"key":"10.1016\/j.ejmech.2013.03.070_bib13e","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.1135245","article-title":"A\u00a0genome-wide association study identifies IL23R as an inflammatory bowel disease gene","volume":"314","author":"Duerr","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14a","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1046\/j.1523-1747.1998.00446.x","article-title":"Expression of interleukin-12 is increased in psoriatic skin","volume":"111","author":"Yawalkar","year":"1998","journal-title":"Journal of Investigative Dermatology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14b","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1084\/jem.20030451","article-title":"Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris","volume":"199","author":"Lee","year":"2004","journal-title":"Journal of Experimental Medicine"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14c","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.4049\/jimmunol.176.3.1908","article-title":"In\u00a0vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin","volume":"176","author":"Piskin","year":"2006","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14d","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/S0016-5085(97)70128-8","article-title":"Interleukin 12 is expressed and actively released by Crohn\u2019s disease intestinal lamina propria mononuclear cells","volume":"112","author":"Monteleone","year":"1997","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14e","first-page":"667","article-title":"Interleukin-12 expression is focally enhanced in the gastric muscosa of pediatric patients with Crohn\u2019s disease","volume":"152","author":"Berrebi","year":"1998","journal-title":"American Journal of Pathology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14f","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/ibd.20475","article-title":"IL-23\/IL-17 immunity as a hallmark of Crohn\u2019s disease","volume":"14","author":"Holtta","year":"2008","journal-title":"Inflammatory Bowel Disease"},{"key":"10.1016\/j.ejmech.2013.03.070_bib14g","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.4049\/jimmunol.180.11.7423","article-title":"Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes","volume":"180","author":"Pene","year":"2008","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15a","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis","volume":"182","author":"van der Fits","year":"2009","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15b","first-page":"597","article-title":"IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation","volume":"118","author":"Ma","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15c","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1053\/j.gastro.2007.03.104","article-title":"Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice","volume":"132","author":"Elson","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15d","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20061099","article-title":"Interleukin-23 drives innate and T cell-mediated intestinal inflammation","volume":"203","author":"Hue","year":"2006","journal-title":"Journal of Experimental Medicine"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15e","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1084\/jem.20061082","article-title":"IL-23 plays a key role in Helicobbacter-induced T cell-dependent colitis","volume":"203","author":"Kullberg","year":"2006","journal-title":"Journal of Experimental Medicine"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15f","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.immuni.2006.05.017","article-title":"Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology","volume":"25","author":"Uhlig","year":"2006","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15g","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1172\/JCI21404","article-title":"IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6","volume":"116","author":"Yen","year":"2006","journal-title":"Journal of Clinical Investigation"},{"key":"10.1016\/j.ejmech.2013.03.070_bib15h","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.4049\/jimmunol.161.6.3143","article-title":"IL-12, but not IFN\u03b3, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice","volume":"161","author":"Davidson","year":"1998","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib16a","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nbt.1903","article-title":"Therapeutic targeting of IL-12\/23 pathways: generation and characterization of ustekinumab","volume":"29","author":"Benson","year":"2011","journal-title":"Nature Biotechnology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib16b","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ni.1803","article-title":"Mixed results with modulation of Th-17 cells in human autoimmune diseases","volume":"11","author":"Steinman","year":"2010","journal-title":"Nature Immunology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0092-8674(00)81166-6","article-title":"Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic response","volume":"93","author":"Rodig","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18a","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1182\/blood.V90.10.3996","article-title":"Structural and functional basis for Jak3-deficient severe combined immunodeficiency","volume":"90","author":"Candotti","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18b","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.270.5237.797","article-title":"Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development","volume":"270","author":"Russell","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18c","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/377065a0","article-title":"Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency","volume":"377","author":"Macchi","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18d","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1126\/science.270.5237.794","article-title":"Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3","volume":"270","author":"Thomis","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18e","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1126\/science.270.5237.800","article-title":"Defective lymphoid development in mice lacking Jak3","volume":"270","author":"Nosaka","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2013.03.070_bib18f","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/1074-7613(95)90066-7","article-title":"Developmental defects of lymphoid cells in Jak3 kinase-deficient mice","volume":"3","author":"Park","year":"1995","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2013.03.070_bib19a","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1600-065X.2008.00644.x","article-title":"Therapeutic targeting of Janus kinases","volume":"223","author":"Pesu","year":"2008","journal-title":"Immunological Reviews"},{"key":"10.1016\/j.ejmech.2013.03.070_bib19b","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1002\/art.24567","article-title":"The safety and efficacy of a JAK inhibitor in patients with cative rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo","volume":"60","author":"Kremer","year":"2009","journal-title":"Arthritis and Rheumatism"},{"key":"10.1016\/j.ejmech.2013.03.070_bib19c","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1038\/jid.2009.25","article-title":"Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis","volume":"129","author":"Boy","year":"2009","journal-title":"Journal of Investigative Dermatology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib20a","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.chembiol.2011.01.012","article-title":"Jak1 has a dominant role over JAK3 in signal transduction through \u03b3c-containing cytokine receptors","volume":"18","author":"Haan","year":"2011","journal-title":"Chemistry & Biology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib20b","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1021\/jm101157q","article-title":"Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family","volume":"54","author":"Thoma","year":"2011","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib21a","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0092-8674(00)81168-X","article-title":"Jak2 deficiency defines an essential development checkpoint in definitive hematopoiesis","volume":"93","author":"Neubauer","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2013.03.070_bib21b","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0092-8674(00)81167-8","article-title":"Jak2 is essential for signaling through a variety of cytokine receptors","volume":"93","author":"Parganas","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2013.03.070_bib21c","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0092-8674(93)90414-L","article-title":"Jak2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin","volume":"74","author":"Witthuhn","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2013.03.070_bib22","unstructured":"S.J. Sohn, K. Barrett, A. Van Abbema, C. Chang, P. Bir Kohli, H. Kanda, J. Smith, Y. Lai, A. Zhou, B. Zhang, W. Yang, K. Williams, C. Macleod, C.A. Hurley, J.J. Kulagowski, N. Lewin-Koh, H.S. Dengler, A.R. Johnson, N. Ghilardi, M. Zak, J. Liang, W.S. Blair, S. Magnuson, L.C. Wu, A restricted role for TYK2 catalytic activity in human cytokine responses, Journal of Immunology, in press."},{"key":"10.1016\/j.ejmech.2013.03.070_bib23a","doi-asserted-by":"crossref","first-page":"8468","DOI":"10.1021\/jm1004286","article-title":"Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection","volume":"53","author":"Flanagan","year":"2010","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib23b","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1182\/blood-2009-04-214957","article-title":"Preclinical characterization of the selective Jak1\/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms","volume":"115","author":"Quintas-Cardama","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2013.03.070_bib23c","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/S0960-894X(02)00106-3","article-title":"Photochemical preparation of a pyridone containing tetracycle: a JAK protein kinase inhibitor","volume":"12","author":"Thompson","year":"2002","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"10.1016\/j.ejmech.2013.03.070_bib24","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/154065804323056495","article-title":"High-throughput screening with quantitation of ATP consumption: a universal non-radioisotope, homogeneous assay for protein kinase","volume":"2","author":"Koresawa","year":"2004","journal-title":"Assay and Drug Development Technologies"},{"key":"10.1016\/j.ejmech.2013.03.070_bib26a","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S1359-6446(05)03386-6","article-title":"Ligand efficiency indices as guideposts for drug discovery","volume":"10","author":"Abad-Zapatero","year":"2005","journal-title":"Drug Discovery Today"},{"key":"10.1016\/j.ejmech.2013.03.070_bib26b","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S1359-6446(04)03069-7","volume":"9","author":"Hopkins","year":"2004","journal-title":"Drug Discovery Today"},{"key":"10.1016\/j.ejmech.2013.03.070_bib26c","doi-asserted-by":"crossref","first-page":"9997","DOI":"10.1073\/pnas.96.18.9997","article-title":"The maximal affinity of ligands","volume":"96","author":"Kuntz","year":"1999","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.ejmech.2013.03.070_bib27a","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1021\/jm021053p","article-title":"A\u00a0comparison of physiochemical property profiles of development and marketed oral drugs","volume":"46","author":"Wenlock","year":"2003","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib27b","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1021\/ci010366a","article-title":"Is there a difference between leads and drugs? A historical perspective","volume":"41","author":"Opera","year":"2001","journal-title":"Journal of Chemical Information and Computer Sciences"},{"key":"10.1016\/j.ejmech.2013.03.070_bib28","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/prot.22889","article-title":"A\u00a0new regulatory switch in a Jak protein kinase","volume":"79","author":"Tsui","year":"2011","journal-title":"Proteins: Structure, Function and Bioinformatics"},{"key":"10.1016\/j.ejmech.2013.03.070_bib30a","unstructured":"Invitrogen, http:\/\/www.invitrogen.com\/site\/us\/en\/home.html?s_kwcid=TC|12295|invitrogen||S|e|14171840346&kw=slivgn (accessed 22.07.12)."},{"key":"10.1016\/j.ejmech.2013.03.070_bib30b","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1089\/154065802761001266","volume":"1","author":"Rodems","year":"2002","journal-title":"Assay and Drug Development Technologies"},{"key":"10.1016\/j.ejmech.2013.03.070_oref2","unstructured":"pKa values were calculated using the MoKa sofware(www.moldiscovery.com) and a customized pKa model."},{"key":"10.1016\/j.ejmech.2013.03.070_bib32a","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1021\/ci700018y","article-title":"New and original pKa prediction method using grid molecular interaction fields","volume":"47","author":"Milletti","year":"2007","journal-title":"Journal of Chemical Information and Modeling"},{"key":"10.1016\/j.ejmech.2013.03.070_bib32b","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1016\/j.ejmech.2010.06.026","article-title":"Extending pKa prediction accuracy: high-throughput pKa measurements to understand pKa modulation of new chemical series","volume":"45","author":"Milletti","year":"2010","journal-title":"European Journal of Medicinal Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib33","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.1021\/jm200349b","article-title":"Selectivity of kinase inhibitor fragments","volume":"54","author":"Bamborough","year":"2011","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib35","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.1021\/jo901609u","article-title":"Synthesis of (NH)m(NMe)4-m-bridged calix[4]pyridines and the effects of NH bridge on structure and properties","volume":"74","author":"Zhang","year":"2009","journal-title":"Journal of Organic Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib36","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1021\/ol016333y","article-title":"Palladium-catalyzed synthesis of arylamines from aryl halides and lithium bis(trimethylsilyl)amide as an ammonia equivalent","volume":"3","author":"Lee","year":"2001","journal-title":"Organic Letters"},{"key":"10.1016\/j.ejmech.2013.03.070_bib39","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.chembiol.2005.04.011","article-title":"Features of selective kinase inhibitors","volume":"12","author":"Knight","year":"2005","journal-title":"Chemistry & Biology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib40","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jmb.2010.05.020","article-title":"Structural and thermodynamic characterization of the Tyk2 and Jak3 kinase domains in complex with CP-690550 and CMP-6","volume":"400","author":"Chrencik","year":"2010","journal-title":"Journal of Molecular Biology"},{"key":"10.1016\/j.ejmech.2013.03.070_bib41","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1107\/S0108768102003890","article-title":"The Cambridge structural database: a quarter of a million crystal structures and rising","volume":"58","author":"Allen","year":"2002","journal-title":"Acta Crystallographica B"},{"key":"10.1016\/j.ejmech.2013.03.070_bib42a","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1021\/ja00328a020","article-title":"Substituent effects on the geometries and energies of cyclopropanes and the corresponding 2-propyl derivatives","volume":"106","author":"Clark","year":"1984","journal-title":"Journal of the American Chemical Society"},{"key":"10.1016\/j.ejmech.2013.03.070_bib42b","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1139\/v82-253","article-title":"Thermochemistry of conjugation of simple cyclopropane derivatives","volume":"60","author":"Fuchs","year":"1982","journal-title":"Canadian Journal of Chemistry"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43a","series-title":"Carbonylamino-substituierte aniline-pyromidinderivative als Tyk-inhibitoren, deren Herstellung und Verwendug als arzneimittel","author":"Buchmann","year":"2009"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43b","series-title":"5,7-Substituted-imidazo[1,2-c]pyrimidines as Inhibitors of JAK Kinases","author":"Boys","year":"2011"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43c","series-title":"Pyridine Compounds and Aza Analogs Thereof as TYK2 Inhibitors","author":"Ellard","year":"2012"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43d","series-title":"Pyrazolopyridines and Pyrazolopyridines and Their Use as Tyk2 Inhibitors","author":"Blench","year":"2012"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43e","series-title":"Azabenzothiazole Compounds, Compositions and Methods of Use","author":"Blench","year":"2012"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43f","series-title":"Imidazopyridine Compounds, Compositions and Methods of Use","author":"Lai","year":"2011"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43g","series-title":"Janus Kinase Inhibitor Compounds and Methods","author":"Goodacre","year":"2010"},{"key":"10.1016\/j.ejmech.2013.03.070_bib43h","series-title":"Triazolopyridines as TYK2 Inhibitors","author":"Ellard","year":"2012"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523413002304?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523413002304?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T19:03:43Z","timestamp":1688238223000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523413002304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":97,"alternative-id":["S0223523413002304"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2013.03.070","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2013,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lead identification of novel and selective TYK2 inhibitors","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2013.03.070","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}