{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:57:14Z","timestamp":1792036634184,"version":"4.4.0"},"reference-count":177,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1007\/s10787-021-00813-y","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T20:04:36Z","timestamp":1621281876000},"page":"617-640","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation"],"prefix":"10.1007","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4974-8568","authenticated-orcid":false,"given":"Namrata P.","family":"Nailwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-0705","authenticated-orcid":false,"given":"Gaurav M.","family":"Doshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"issue":"5573","key":"813_CR1","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1126\/science.1071545","volume":"296","author":"DS Aaronson","year":"2002","unstructured":"Aaronson DS, Horvath CM (2002) A road map for those who don\u2019t know JAK-STAT. Science 296(5573):1653\u20131655. https:\/\/doi.org\/10.1126\/science.1071545","journal-title":"Science"},{"issue":"5","key":"813_CR2","doi-asserted-by":"publisher","first-page":"627","DOI":"10.14202\/vetworld.2018.627-635","volume":"11","author":"LA Abdulkhaleq","year":"2018","unstructured":"Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM (2018) The crucial roles of inflammatory mediators in inflammation: a review. Vet World 11(5):627\u2013635. https:\/\/doi.org\/10.14202\/vetworld.2018.627-635","journal-title":"Vet World"},{"issue":"35","key":"813_CR3","doi-asserted-by":"publisher","first-page":"27414","DOI":"10.1074\/jbc.M004810200","volume":"275","author":"A Adams","year":"2000","unstructured":"Adams A, Thorn JM, Yamabhai M, Kay BK, O'Bryan JP (2000) Intersectin, an adaptor protein involved in clathrin-mediated endocytosis, activates mitogenic signaling pathways. J Biol Chem 275(35):27414\u201327420. https:\/\/doi.org\/10.1074\/jbc.M004810200","journal-title":"J Biol Chem"},{"issue":"1","key":"813_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1756-8722-6-27","volume":"6","author":"A Akinleye","year":"2013","unstructured":"Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D (2013) MEK and the inhibitors: from bench to bedside. J Hematol Oncol 6(1):1\u201311. https:\/\/doi.org\/10.1186\/1756-8722-6-27","journal-title":"J Hematol Oncol"},{"issue":"5","key":"813_CR5","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1084\/jem.191.5.859","volume":"191","author":"M Allen","year":"2000","unstructured":"Allen M, Svensson L, Roach M, Hambor J, McNeish J, Gabel CA (2000) Deficiency of the stress kinase p38\u03b1 results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells. J Exp Med 191(5):859\u2013869. https:\/\/doi.org\/10.1084\/jem.191.5.859","journal-title":"J Exp Med"},{"key":"813_CR6","doi-asserted-by":"publisher","first-page":"113109","DOI":"10.1016\/j.ejmech.2020.113109","volume":"211","author":"RM \u00c1lvarez","year":"2021","unstructured":"\u00c1lvarez RM, Garc\u00eda BA, Fagundo RC (2021) Omipalisib inspired macrocycles as dual PI3K\/mTOR inhibitors. Eur J Med Chem 211:113109. https:\/\/doi.org\/10.1016\/j.ejmech.2020.113109","journal-title":"Eur J Med Chem"},{"issue":"1","key":"813_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-019-0079-0","volume":"4","author":"SS Athari","year":"2019","unstructured":"Athari SS (2019) Targeting cell signaling in allergic asthma. Signal Transduct Target Ther 4(1):1\u201319. https:\/\/doi.org\/10.1038\/s41392-019-0079-0","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"813_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20140712","volume":"462","author":"JJ Babon","year":"2014","unstructured":"Babon JJ, Lucet IS, Murphy JM, Nicola NA, Varghese LN (2014) The molecular regulation of Janus kinase (JAK) activation. Biochem J 462(1):1\u201313. https:\/\/doi.org\/10.1042\/BJ20140712","journal-title":"Biochem J"},{"issue":"47","key":"813_CR9","doi-asserted-by":"publisher","first-page":"27995","DOI":"10.1074\/jbc.270.47.27995","volume":"270","author":"S Bagrodia","year":"1995","unstructured":"Bagrodia S, Derijard B, Davis RJ, Cerione RA (1995) Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem 270(47):27995\u201327998. https:\/\/doi.org\/10.1074\/jbc.270.47.27995","journal-title":"J Biol Chem"},{"issue":"6","key":"813_CR10","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.3390\/ph3061842","volume":"3","author":"MC Bagley","year":"2010","unstructured":"Bagley MC, Davis T, Murziani SGP, Widdowson SC, Kipling D (2010) Use of p38 MAPK inhibitors for the treatment of Werner syndrome. Pharmaceuticals 3(6):1842\u20131872. https:\/\/doi.org\/10.3390\/ph3061842","journal-title":"Pharmaceuticals"},{"issue":"24","key":"813_CR11","doi-asserted-by":"publisher","first-page":"6501","DOI":"10.1016\/j.bmcl.2008.10.054","volume":"18","author":"SD Barrett","year":"2008","unstructured":"Barrett SD, Bridges AJ, Dudley DT et al (2008) The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Bioorg Med Chem Lett 18(24):6501\u20136504. https:\/\/doi.org\/10.1016\/j.bmcl.2008.10.054","journal-title":"Bioorg Med Chem Lett"},{"issue":"4","key":"813_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.21873\/cgp.20082","volume":"15","author":"D Basu","year":"2018","unstructured":"Basu D, Salgado CM, Bauer B, Khakoo Y, Patel JR, Hoehl RM, Bertolini DM, Zabec J, Brzozowski MR, Reyes-M\u00fagica M (2018) The dual PI3K\/mTOR inhibitor omipalisib\/GSK2126458 inhibits clonogenic growth in oncogenically-transformed cells from neurocutaneous melanocytosis. Cancer Genom Proteomics 15(4):239\u2013248. https:\/\/doi.org\/10.21873\/cgp.20082","journal-title":"Cancer Genom Proteomics"},{"issue":"5","key":"813_CR13","doi-asserted-by":"publisher","first-page":"433","DOI":"10.4062\/biomolther.2012.20.5.433","volume":"20","author":"S Batbayar","year":"2012","unstructured":"Batbayar S, Lee DH, Kim HW (2012) Immunomodulation of fungal \u03b2-glucan in host defense signaling by dectin-1. Biomol Ther 20(5):433\u2013445. https:\/\/doi.org\/10.4062\/biomolther.2012.20.5.433","journal-title":"Biomol Ther"},{"key":"813_CR14","doi-asserted-by":"publisher","unstructured":"Bernhardi RV (2008) Neurodegenerative diseases\u2014MAPK signalling pathways in neuroinflammation. Encycl Neurosci 2614\u20132620. https:\/\/doi.org\/10.1007\/978-3-540-29678-2_3820. Accessed on 9 August 2020","DOI":"10.1007\/978-3-540-29678-2_3820"},{"key":"813_CR15","unstructured":"Blatt LM, Seiwert SD, Beigelman LD, Radhakrishnan R, Kossen K, Serebryany V (2018) Method of modulating stress-activated protein kinase system. US10010536B2. https:\/\/patents.google.com\/patent\/US10010536B2. Accessed 13 Aug 2020"},{"issue":"16","key":"813_CR16","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1101\/gad.1107303","volume":"17","author":"D Brancho","year":"2003","unstructured":"Brancho D, Tanaka N, Jaeschke A, Ventura JJ, Kelkar N, Tanaka Y, Kyuuma M, Takeshita T, Flavell RA, Davis RJ (2003) Mechanism of p38 MAP kinase activation in vivo. Genes Dev 17(16):1969\u20131978. https:\/\/doi.org\/10.1101\/gad.1107303","journal-title":"Genes Dev"},{"key":"813_CR17","unstructured":"Broeckx R, Charron CE, Copmans A, Filliers W, Ito K, King-Underwood J, Longshaw AI, Onions ST (2016) 1-Pyrazolyl-3-(4-((2-anilinopyrimidin-4-Yl)oxy)napththalen-1-Yl) ureas as P38 MAP kinase inhibitors. AU2012320300B2. https:\/\/patents.google.com\/patent\/AU2012320300B2. Accessed on 13 Aug 2020"},{"issue":"8","key":"813_CR18","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1007\/s00125-016-4021-5","volume":"59","author":"FC Brosius","year":"2016","unstructured":"Brosius FC, Tuttle KR, Kretzler M (2016) JAK inhibition in the treatment of diabetic kidney disease. Diabetologia 59(8):1624\u20131627. https:\/\/doi.org\/10.1007\/s00125-016-4021-5","journal-title":"Diabetologia"},{"key":"813_CR19","volume-title":"Goodman & Gilman\u2019s the pharmacological basis of therapeutics","author":"L Brunton","year":"2018","unstructured":"Brunton L, Dandan R, Knollmann B (2018) Goodman & Gilman\u2019s the pharmacological basis of therapeutics, 13th edn. McGraw-Hill Medical, USA","edition":"13"},{"key":"813_CR20","unstructured":"Cariou CAM, Charron CE, Fordyce EFA, Hamza D, Fyfe MCT, Ito K, King-Underwood J, Murray PJ, Onions ST, Thom SM, Watson HTA, Williams JG (2017) Pyrazolyl-ureas as kinase inhibitors. US9701670B2. https:\/\/patents.google.com\/patent\/US9701670B2. Accessed 13 Aug 2020"},{"issue":"13","key":"813_CR21","doi-asserted-by":"publisher","first-page":"6910","DOI":"10.1073\/pnas.94.13.6910","volume":"94","author":"M Chen","year":"1997","unstructured":"Chen M, Cheng A, Chen YQ, Hymel A, Hanson EP, Kimmel L, Minami Y, Taniguchi T, Changelian PS, O\u2019Shea JJ (1997) The amino terminus of JAK3 is necessary and sufficient for binding to the common \u03b3 chain and confers the ability to transmit interleukin 2-mediated signals. Proc Natl Acad Sci USA 94(13):6910\u20136915. https:\/\/doi.org\/10.1073\/pnas.94.13.6910","journal-title":"Proc Natl Acad Sci USA"},{"key":"813_CR23","unstructured":"ClinicalTrials.gov (2018a) A phase II study in patients with moderate to severe active crohn\u2019s disease. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03677648. Accessed 13 August 2020"},{"key":"813_CR24","unstructured":"ClinicalTrials.gov (2018b) A phase II study in patients with moderate to severe active ulcerative colitis. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03675477. Accessed 13 August 2020"},{"key":"813_CR25","unstructured":"ClinicalTrials.gov (2018c) A study to evaluate the safety and efficacy of tofacitinib modified release tablets compared to tofacitinib immediate release tablets in adult patients with rheumatoid arthritis. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02281552. Accessed 13 August 2020"},{"key":"813_CR26","unstructured":"ClinicalTrials.gov (2017a) Discovery of sirolimus sensitive biomarkers in blood. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03304678. Accessed 13 August 2020"},{"key":"813_CR27","unstructured":"ClinicalTrials.gov (2018d) Effect of the inhibitors of the way JAK-STAT on regulatory B cells. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03755297. Accessed 13 August 2020"},{"key":"813_CR28","unstructured":"ClinicalTrials.gov (2019a) Evaluation of pain sensitization in rheumatoid arthritis: analysis on a cohort of tofacitinib treated patients. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03815578. Accessed 13 August 2020"},{"key":"813_CR29","unstructured":"ClinicalTrials.gov (2016) In vitro evaluation of a novel drug on airway epithelial cells obtained from participants with severe asthma. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02740049. Accessed 13 August 2020"},{"key":"813_CR30","unstructured":"ClinicalTrials.gov (2008) P38 mitogen\u2212activated protein kinase (MAPK) and steroid insensitivity in asthma. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00676572. Accessed 13 August 2020"},{"key":"813_CR31","unstructured":"ClinicalTrials.gov (2017b) Sirolimus for autoimmune disease of blood cells. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00392951. Accessed on 13 August 2020"},{"key":"813_CR32","unstructured":"ClinicalTrials.gov (2004) Study evaluating CCI-779 in active rheumatoid arthritis on concomitant methotrexate therapy. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00076206. Accessed 13 August 2020"},{"key":"813_CR33","unstructured":"ClinicalTrials.gov (2019b) Subunit vaccine against herpes zoster in RA patients treated with JAK-inhibitors (VACCIMIL-ZOSTER). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03886038. Accessed 13 August 2020"},{"key":"813_CR34","unstructured":"ClinicalTrials.gov (2019c) Tocilizumab REMission in early RA. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04157010. Accessed 13 August 2020"},{"key":"813_CR35","unstructured":"Cooper GM (2000) Signaling molecules and their receptors. The cell: a molecular approach, 2nd edn. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK9924\/. Accessed 5 August 2020"},{"key":"813_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.phrs.2013.06.007","volume":"76","author":"M Coskun","year":"2013","unstructured":"Coskun M, Salem M, Pedersen J, Nielsen OH (2013) Involvement of JAK\/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res 76:1\u20138. https:\/\/doi.org\/10.1016\/j.phrs.2013.06.007","journal-title":"Pharmacol Res"},{"issue":"1","key":"813_CR37","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","volume":"335","author":"AE Coutinho","year":"2011","unstructured":"Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments, and mechanistic insights. Mol Cell Endocrinol 335(1):2\u201313","journal-title":"Mol Cell Endocrinol"},{"issue":"3","key":"813_CR38","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1186\/ar4174","volume":"15","author":"LJ Crofford","year":"2013","unstructured":"Crofford LJ (2013) Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 15(3):S2. https:\/\/doi.org\/10.1186\/ar4174","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"813_CR39","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1158\/1535-7163.MCT-09-0601","volume":"9","author":"S Daouti","year":"2010","unstructured":"Daouti S, Higgins B, Kolinsky K et al (2010) Preclinical in vivo evaluation of efficacy, pharmacokinetics, and pharmacodynamics of a novel MEK1\/2 kinase inhibitor RO5068760 in multiple tumor models. Mol Cancer Ther 9(1):134\u2013144. https:\/\/doi.org\/10.1158\/1535-7163.MCT-09-0601","journal-title":"Mol Cancer Ther"},{"key":"813_CR40","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.3389\/fnins.2019.01018","volume":"13","author":"BG de Freitas","year":"2019","unstructured":"de Freitas BG, Pereira ML, Cec\u00edlia SVF, H\u00f6sch GN, Picolo G, Cury Y, Zambelli OV (2019) Mitogen-activated protein kinase signaling mediates morphine induced-delayed hyperalgesia. Front Neurosci 13:1018. https:\/\/doi.org\/10.3389\/fnins.2019.01018","journal-title":"Front Neurosci"},{"key":"813_CR41","unstructured":"Demopulos G, Palmer PP, Herz JM (2006a) Irrigation solution and method for inhibition of pain and inflammation. US20060229588A1. https:\/\/patents.google.com\/patent\/US20060229588A1. Accessed 13 Aug 2020"},{"key":"813_CR42","unstructured":"Demopulos GA, Palmer PP, Herz JM (2006b) Method of inhibition of pain and inflammation during surgery comprising administration of soluble TNF receptors. US7091181B2. https:\/\/patents.google.com\/patent\/US7091181B2. Accessed 13 Aug 2020"},{"key":"813_CR43","doi-asserted-by":"publisher","unstructured":"Deng Y, Hahn BH, Tsao BP (2013) Systemic lupus erythematosus. Emery and Rimoin\u2019s principles and practice of medical genetics 1\u201322. https:\/\/doi.org\/10.1016\/B978-0-12-383834-6.00081-1. Accessed 15 July 2020","DOI":"10.1016\/B978-0-12-383834-6.00081-1"},{"issue":"5","key":"813_CR44","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1016\/j.bmcl.2011.01.071","volume":"21","author":"Q Dong","year":"2011","unstructured":"Dong Q, Dougan DR, Gong X, Halkowycz P, Jin B, Kanouni T, O\u2019Connell SM, Scorah N, Shi L, Wallace MB, Zhou F (2011) Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett 21(5):1315\u20131319. https:\/\/doi.org\/10.1016\/j.bmcl.2011.01.071","journal-title":"Bioorg Med Chem Lett"},{"issue":"14","key":"813_CR45","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","volume":"14","author":"DS Dos","year":"2004","unstructured":"Dos DS, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14(14):1296\u20131302. https:\/\/doi.org\/10.1016\/j.cub.2004.06.054","journal-title":"Curr Biol"},{"issue":"3","key":"813_CR46","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.bbapap.2009.12.001","volume":"1804","author":"RJO Dowling","year":"2010","unstructured":"Dowling RJO, Topisirovic I, Fonseca BD, Sonenberg N (2010) Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Et Biophys Acta Proteins Proteomics 1804(3):433\u2013439. https:\/\/doi.org\/10.1016\/j.bbapap.2009.12.001","journal-title":"Biochim Et Biophys Acta Proteins Proteomics"},{"issue":"1","key":"813_CR47","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1042\/CS20020240","volume":"104","author":"JS Duffield","year":"2003","unstructured":"Duffield JS (2003) The inflammatory macrophage: a story of Jekyll and Hyde. Clin Sci (lond) 104(1):27\u201338","journal-title":"Clin Sci (lond)"},{"key":"813_CR48","unstructured":"Elsner J, Harris RL, Lee B, et al (2019) MTOR kinase inhibitor for tumour indication relevant to MTOR\/PI3K\/AKT\/approach and disease. CN104725384B. https:\/\/patents.google.com\/patent\/CN104725384B. Accessed 13 Aug 2020"},{"key":"813_CR49","doi-asserted-by":"publisher","unstructured":"Ferrao R, Lupardus PJ (2017) The Janus Kinase (JAK) FERM and SH2 domains: bringing specificity to JAK-receptor interactions. Front Endocrinol 8(APR):1. https:\/\/doi.org\/10.3389\/fendo.2017.00071. Accessed 5 August 2020","DOI":"10.3389\/fendo.2017.00071"},{"issue":"2","key":"813_CR50","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/j.1365-2249.2006.03261.x","volume":"147","author":"L Ferrero-Miliani","year":"2007","unstructured":"Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1\u03b2 generation. Clin Exp Immunol 147(2):227\u2013235. https:\/\/doi.org\/10.1111\/j.1365-2249.2006.03261.x","journal-title":"Clin Exp Immunol"},{"key":"813_CR51","unstructured":"Fordyce EAF, King-Underwood J, Longshaw AI, Onions ST, Venable JD (2019). Aromatic heterocyclic compounds as antiinflammatory compounds. AU2015216957B2. https:\/\/patents.google.com\/patent\/AU2015216957B2. Accessed 9 Aug 2020"},{"issue":"5","key":"813_CR52","doi-asserted-by":"publisher","first-page":"e33984","DOI":"10.1371\/journal.pone.0033984","volume":"7","author":"K Fredriksson","year":"2012","unstructured":"Fredriksson K, Fielhaber JA, Lam JK, Yao X, Meyer KS, Keeran KJ, Zywicke GJ, Qu X, Yu ZX, Moss J, Kristof AS, Levine SJ (2012) Paradoxical effects of Rapamycin on experimental house dust mite-induced asthma. PLoS ONE 7(5):e33984. https:\/\/doi.org\/10.1371\/journal.pone.0033984","journal-title":"PLoS ONE"},{"issue":"9","key":"813_CR53","doi-asserted-by":"publisher","first-page":"5298","DOI":"10.4049\/jimmunol.0902819","volume":"184","author":"JS Fridman","year":"2010","unstructured":"Fridman JS, Scherle PA, Collins R et al (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol 184(9):5298\u20135307. https:\/\/doi.org\/10.4049\/jimmunol.0902819","journal-title":"J Immunol"},{"issue":"3","key":"813_CR54","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2174\/1568010054022024","volume":"4","author":"N Fujiwara","year":"2005","unstructured":"Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4(3):281\u2013286. https:\/\/doi.org\/10.2174\/1568010054022024","journal-title":"Curr Drug Targets Inflamm Allergy"},{"issue":"7","key":"813_CR55","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1074\/mcp.M300131-MCP200","volume":"3","author":"Q Gao","year":"2004","unstructured":"Gao Q, Hua J, Kimura R, Headd JJ, Fu XY, Chin EY (2004) Identification of the linker-SH2 domain of STAT as the origin of the SH2 domain using two-dimensional structural alignment. Mol Cell Proteomics 3(7):704\u2013714. https:\/\/doi.org\/10.1074\/mcp.M300131-MCP200","journal-title":"Mol Cell Proteomics"},{"key":"813_CR56","doi-asserted-by":"publisher","first-page":"34391","DOI":"10.1074\/jbc.273.51.34391","volume":"273","author":"J Garcia","year":"1998","unstructured":"Garcia J, Lemercier B, Roman-Roman S, Rawadi G (1998) A mycoplasma fermentans-derived synthetic lipopeptide induces AP-1 and NF-\u03baB activity and cytokine secretion in macrophages via the activation of mitogen-activated protein kinase pathways. J Biol Chem 273:34391\u201334398","journal-title":"J Biol Chem"},{"key":"813_CR57","unstructured":"Genecards.org (n.d.) STAT5A Protein. https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=STAT5A. Accessed 8 Dec 2020"},{"issue":"5","key":"813_CR58","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1158\/1078-0432.CCR-10-2200","volume":"17","author":"AG Gilmartin","year":"2011","unstructured":"Gilmartin AG, Bleam MR, Groy A et al (2011) GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 17(5):989\u20131000. https:\/\/doi.org\/10.1158\/1078-0432.CCR-10-2200","journal-title":"Clin Cancer Res"},{"issue":"9","key":"813_CR59","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1093\/protein\/15.9.727","volume":"15","author":"F Giordanetto","year":"2002","unstructured":"Giordanetto F, Kroemer RT (2002) Prediction of the structure of human Janus kinase 2 (JAK2) comprising JAK homology domains 1 through 7. Protein Eng 15(9):727\u2013737. https:\/\/doi.org\/10.1093\/protein\/15.9.727","journal-title":"Protein Eng"},{"issue":"8","key":"813_CR60","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1093\/emboj\/17.8.2224","volume":"17","author":"JD Graves","year":"1998","unstructured":"Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DKM, Wright M, Chernoff J, Clark E, Krebs EG (1998) Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J 17(8):2224\u20132234. https:\/\/doi.org\/10.1093\/emboj\/17.8.2224","journal-title":"EMBO J"},{"issue":"1","key":"813_CR61","doi-asserted-by":"publisher","first-page":"339","DOI":"10.4049\/jimmunol.1303356","volume":"195","author":"Y Guan","year":"2015","unstructured":"Guan Y, Zhang L, Li X et al (2015) Repression of mammalian target of rapamycin complex 1 inhibits intestinal regeneration in acute inflammatory bowel disease models. J Immunol 195(1):339\u2013346. https:\/\/doi.org\/10.4049\/jimmunol.1303356","journal-title":"J Immunol"},{"issue":"1","key":"813_CR62","doi-asserted-by":"publisher","first-page":"5906","DOI":"10.1182\/blood-2019-127272","volume":"134","author":"VA Guerra","year":"2019","unstructured":"Guerra VA, Kantarjian HM, Borthakur GM, Verstovsek S, Pike A, Ravandi F, Jabbour E, Cortes JE (2019) A phase I\u2013II study of ruxolitinib (INCB18424) for patients with chronic myeloid leukemia with minimal residual disease while on therapy with imatinib. Blood 134(1):5906\u20135906. https:\/\/doi.org\/10.1182\/blood-2019-127272","journal-title":"Blood"},{"issue":"11","key":"813_CR63","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1158\/1535-7163.MCT-15-0365","volume":"14","author":"SM Guichard","year":"2015","unstructured":"Guichard SM, Curwen J, Bihani T (2015) AZD2014, an inhibitor of mTORC1 and mTORC2, is highly effective in ER+ breast cancer when administered using intermittent or continuous schedules. Mol Cancer Ther 14(11):2508\u20132518. https:\/\/doi.org\/10.1158\/1535-7163.MCT-15-0365","journal-title":"Mol Cancer Ther"},{"issue":"20","key":"813_CR64","doi-asserted-by":"publisher","first-page":"5601","DOI":"10.1093\/emboj\/18.20.5601","volume":"18","author":"KC Goh","year":"1999","unstructured":"Goh KC, Haque SJ, Williams BRG (1999) p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons. EMBO J 18(20):5601\u20135608. https:\/\/doi.org\/10.1093\/emboj\/18.20.5601","journal-title":"EMBO J"},{"issue":"7466","key":"813_CR65","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/nature12441","volume":"501","author":"G Hatzivassiliou","year":"2013","unstructured":"Hatzivassiliou G, Haling JR, Chen H et al (2013) Mechanism of MEK inhibition determines efficacy in mutant KRAS-versus BRAF-driven cancers. Nature 501(7466):32\u2013236. https:\/\/doi.org\/10.1038\/nature12441","journal-title":"Nature"},{"issue":"3","key":"813_CR66","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1124\/jpet.108.139006","volume":"327","author":"RJ Hill","year":"2008","unstructured":"Hill RJ, Dabbagh K, Phippard D et al (2008) Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity. J Pharmacol Exp Ther 327(3):610\u2013619. https:\/\/doi.org\/10.1124\/jpet.108.139006","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"813_CR67","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.1749-6632.2010.05907.x","volume":"1217","author":"LM Heltemes-Harris","year":"2011","unstructured":"Heltemes-Harris LM, Willette MJL, Vang KB, Farrar MA (2011) The role of STAT5 in the development, function, and transformation of B and T lymphocytes. Ann N Y Acad Sci 1217(1):18\u201331. https:\/\/doi.org\/10.1111\/j.1749-6632.2010.05907.x","journal-title":"Ann N Y Acad Sci"},{"key":"813_CR68","doi-asserted-by":"publisher","unstructured":"Hong Z, Hong Z, Wu D, Nie H (2016) Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model. Mol Cell Biochem 419(1\u20132). https:\/\/doi.org\/10.1007\/s11010-0162722-1","DOI":"10.1007\/s11010-0162722-1"},{"issue":"1","key":"813_CR69","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jaci.2015.11.024","volume":"138","author":"V Hox","year":"2016","unstructured":"Hox V, O\u2019Connell MP, Lyons JJ et al (2016) Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol 138(1):187\u2013199. https:\/\/doi.org\/10.1016\/j.jaci.2015.11.024","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"813_CR70","doi-asserted-by":"publisher","first-page":"154564","DOI":"10.1371\/journal.pone.0154564","volume":"11","author":"S Hu","year":"2016","unstructured":"Hu S, Chen M, Wang Y et al (2016) mTOR inhibition attenuates dextran sulfate sodium-induced colitis by suppressing T cell proliferation and balancing TH1\/TH17\/Treg profile. PLoS ONE 11(4):154564. https:\/\/doi.org\/10.1371\/journal.pone.0154564","journal-title":"PLoS ONE"},{"issue":"45","key":"813_CR71","doi-asserted-by":"publisher","first-page":"6087","DOI":"10.1038\/sj.onc.1203129","volume":"18","author":"H Ichijo","year":"1999","unstructured":"Ichijo H (1999) From receptors to stress-activated MAP kinases. Oncogene 18(45):6087\u20136093. https:\/\/doi.org\/10.1038\/sj.onc.1203129","journal-title":"Oncogene"},{"issue":"5296","key":"813_CR72","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1126\/science.275.5296.90","volume":"275","author":"H Ichijo","year":"1997","unstructured":"Ichijo H, Nishida E, Irie K, Ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, Gotoh Y (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK\/JNK and p38 signaling pathways. Science 275(5296):90\u201394. https:\/\/doi.org\/10.1126\/science.275.5296.90","journal-title":"Science"},{"issue":"9","key":"813_CR73","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/PL00000267","volume":"50","author":"P Igaz","year":"2001","unstructured":"Igaz P, T\u00f3th S, Falus A (2001) Biological and clinical significance of the JAK-STAT pathway; lessons from knockout mice. Inflamm Res 50(9):435\u2013441. https:\/\/doi.org\/10.1007\/PL00000267","journal-title":"Inflamm Res"},{"issue":"2","key":"813_CR74","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0955-0674(98)80143-9","volume":"10","author":"YT Ip","year":"1998","unstructured":"Ip YT, Davis RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK)\u2014from inflammation to development. Curr Opin Cell Biol 10(2):205\u2013219. https:\/\/doi.org\/10.1016\/S0955-0674(98)80143-9","journal-title":"Curr Opin Cell Biol"},{"issue":"1","key":"813_CR75","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.cell.2006.08.033","volume":"127","author":"E Jacinto","year":"2006","unstructured":"Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B (2006) SIN1\/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127(1):125\u2013137. https:\/\/doi.org\/10.1016\/j.cell.2006.08.033","journal-title":"Cell"},{"issue":"11","key":"813_CR76","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/ncb1183","volume":"6","author":"E Jacinto","year":"2004","unstructured":"Jacinto E, Loewith R, Schmidt A, Lin S, R\u00fcegg MA, Hall A, Hall MN (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6(11):1122\u20131128. https:\/\/doi.org\/10.1038\/ncb1183","journal-title":"Nat Cell Biol"},{"issue":"10","key":"813_CR77","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1177\/1947601910397187","volume":"1","author":"SS Jatiani","year":"2010","unstructured":"Jatiani SS, Baker SJ, Silverman LR, Premkumar Reddy E (2010) JAK\/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer 1(10):979\u2013993. https:\/\/doi.org\/10.1177\/1947601910397187","journal-title":"Genes Cancer"},{"issue":"5","key":"813_CR78","doi-asserted-by":"publisher","first-page":"457","DOI":"10.4062\/biomolther.2012.20.5.457","volume":"20","author":"JJ Jeong","year":"2012","unstructured":"Jeong JJ, Jang SE, Joh EH, Han MJ, Kim DH (2012) Kalopanaxsaponin B ameliorates TNBS-induced colitis in mice. Biomol Ther 20(5):457\u2013462. https:\/\/doi.org\/10.4062\/biomolther.2012.20.5.457","journal-title":"Biomol Ther"},{"key":"813_CR79","unstructured":"Jordi, Batch, Luis T, Miquel, Pajes, Santa C, Tartaburu, Morpole, Robert, Eastwood J, Gonzalez, Rodriguez V, Julio, Matassa (2015) Pyrazole derivatives as JAK inhibitors. JP5820400B2. https:\/\/patents.google.com\/patent\/JP5820400B2. Accessed 9 Aug 2020"},{"key":"813_CR80","unstructured":"Jordi, Batch, Luis T, Miquel, Pajes, Santa C, Tartaburu, Morpole, Robert, Eastwood J, Gonzalez, Rodriguez V, Julio, Matassa (2016) Respiratory preparation containing P38 MAPK inhibitor. JP5973426B2. https:\/\/patents.google.com\/patent\/JP5973426B2. Accessed 9 Aug 2020"},{"key":"813_CR81","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/421821","author":"MZ Kamran","year":"2013","unstructured":"Kamran MZ, Patil P, Gude RP (2013) Role of STAT3 in cancer metastasis and translational advances. Biomed Res Int. https:\/\/doi.org\/10.1155\/2013\/421821","journal-title":"Biomed Res Int"},{"issue":"2\u20133","key":"813_CR82","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1385\/ir:21:2-3:233","volume":"21","author":"Y Kato","year":"2000","unstructured":"Kato Y, Chao TH, Hayashi M, Tapping RI, Lee JD (2000) Role of BMK1 in the regulation of growth factor-induced cellular responses. Immunol Res 21(2\u20133):233\u2013237. https:\/\/doi.org\/10.1385\/ir:21:2-3:233","journal-title":"Immunol Res"},{"issue":"6","key":"813_CR83","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1136\/annrheumdis-2016-210105","volume":"76","author":"A Kavanaugh","year":"2017","unstructured":"Kavanaugh A, Kremer J, Ponce L, Cseuz R, Reshetko OV, Stanislavchuk M, Greenwald M, Van Der Aa A, Vanhoutte F, Tasset C, Harrison P (2017) Filgotinib (GLPG0634\/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomized, dose-finding study (DARWIN 2). Ann Rheum Dis 76(6):1009\u20131019. https:\/\/doi.org\/10.1136\/annrheumdis-2016-210105","journal-title":"Ann Rheum Dis"},{"key":"813_CR84","volume-title":"Pathology: the big picture","author":"W Kemp","year":"2007","unstructured":"Kemp W, Burns D, Brown T (2007) Pathology: the big picture. McGraw-Hill Medical, USA"},{"issue":"4","key":"813_CR85","doi-asserted-by":"publisher","first-page":"401","DOI":"10.5142\/jgr.2013.37.401","volume":"37","author":"HM Ko","year":"2013","unstructured":"Ko HM, Joo SH, Kim P, Park JH, Kim HJ, Ho Bahn G, Kim HY, Lee J, Han SH, Shin CY, Park SH (2013) Effects of Korean Red Ginseng extract on tissue plasminogen activator and plasminogen activator inhibitor-1 expression in cultured rat primary astrocytes. J Ginseng Res 37(4):401\u2013412. https:\/\/doi.org\/10.5142\/jgr.2013.37.401","journal-title":"J Ginseng Res"},{"key":"813_CR86","doi-asserted-by":"publisher","unstructured":"Kurdi A, De Meyer GRY, Martinet W (2016) Potential therapeutic effects of mTOR inhibition in atherosclerosis. Br J Clin Pharmacol 1267\u20131279. https:\/\/doi.org\/10.1111\/bcp.12820. Accessed 11 August 2020","DOI":"10.1111\/bcp.12820"},{"key":"813_CR87","doi-asserted-by":"publisher","unstructured":"Kurita Y, Araya J, Minagawa S (2017) Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy. Respir Res 18(1). https:\/\/doi.org\/10.1186\/s12931-017-0600-3","DOI":"10.1186\/s12931-017-0600-3"},{"issue":"3","key":"813_CR88","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2340\/00015555-1046","volume":"91","author":"L Langer Lilleholt","year":"2011","unstructured":"Langer Lilleholt L, Johansen C, Arthur JSC, Funding A, Bibby BM, Kragballe K, Iversen L (2011) Role of p38 mitogen-activated protein kinase isoforms in murine skin inflammation induced by 12-O-tetradecanoylphorbol 13-acetate. Acta Dermatol Venereolog 91(3):271\u2013278. https:\/\/doi.org\/10.2340\/00015555-1046","journal-title":"Acta Dermatol Venereolog"},{"issue":"20","key":"813_CR89","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1242\/jcs.051011","volume":"122","author":"M Laplante","year":"2009","unstructured":"Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122(20):3589\u20133594. https:\/\/doi.org\/10.1242\/jcs.051011","journal-title":"J Cell Sci"},{"issue":"1","key":"813_CR90","doi-asserted-by":"publisher","first-page":"232","DOI":"10.2174\/1874312901206010232","volume":"6","author":"A Laurence","year":"2012","unstructured":"Laurence A (2012) JAK kinases in health and disease: an update. Open Rheumatol J 6(1):232\u2013244. https:\/\/doi.org\/10.2174\/1874312901206010232","journal-title":"Open Rheumatol J"},{"issue":"8","key":"813_CR91","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.3390\/molecules22081287","volume":"22","author":"JK Lee","year":"2017","unstructured":"Lee JK, Kim NJ (2017) Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer\u2019s disease. Molecules 22(8):1287. https:\/\/doi.org\/10.3390\/molecules22081287","journal-title":"Molecules"},{"issue":"3","key":"813_CR92","doi-asserted-by":"publisher","first-page":"146","DOI":"10.2174\/157340810793384124","volume":"6","author":"CS Lee","year":"2010","unstructured":"Lee CS, Duesbery NS (2010) Highly selective MEK inhibitors. Curr Enzym Inhib 6(3):146\u2013157. https:\/\/doi.org\/10.2174\/157340810793384124","journal-title":"Curr Enzym Inhib"},{"issue":"7","key":"813_CR93","doi-asserted-by":"publisher","first-page":"e0131400","DOI":"10.1371\/journal.pone.0131400","volume":"10","author":"EY Leung","year":"2015","unstructured":"Leung EY, Askarian-Amiri M, Finlay GJ, Rewcastle GW, Baguley BC (2015) Potentiation of growth inhibitory responses of the mTOR inhibitor everolimus by dual mTORC1\/2 inhibitors in cultured breast cancer cell lines. PLoS ONE 10(7):e0131400. https:\/\/doi.org\/10.1371\/journal.pone.0131400","journal-title":"PLoS ONE"},{"issue":"9","key":"813_CR94","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1172\/jci15650","volume":"109","author":"DE Levy","year":"2002","unstructured":"Levy DE, Lee C (2002) What does Stat3 do? J Clin Investig 109(9):1143\u20131148. https:\/\/doi.org\/10.1172\/jci15650","journal-title":"J Clin Investig"},{"key":"813_CR95","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1155\/2012\/146154","volume":"2012","author":"AKH Lim","year":"2012","unstructured":"Lim AKH, Tesch GH (2012) Inflammation in diabetic nephropathy. Mediators Inflamm 2012:12. https:\/\/doi.org\/10.1155\/2012\/146154","journal-title":"Mediators Inflamm"},{"issue":"3","key":"813_CR96","doi-asserted-by":"publisher","first-page":"e32777","DOI":"10.1371\/journal.pone.0032777","volume":"7","author":"C Liongue","year":"2012","unstructured":"Liongue C, O\u2019Sullivan LA, Trengove MC, Ward AC (2012) Evolution of JAK-STAT pathway components: mechanisms and role in immune system development. PLoS ONE 7(3):e32777. https:\/\/doi.org\/10.1371\/journal.pone.0032777","journal-title":"PLoS ONE"},{"key":"813_CR97","unstructured":"Li P, Wang D, Wu Y, Ganfeng C, Gaya M (2019) Processes and intermediates for making a Jak inhibitor. TWI634121B. https:\/\/patents.google.com\/patent\/TWI634121B. Accessed 8 Aug 2020"},{"key":"813_CR98","doi-asserted-by":"publisher","unstructured":"Loh CY, Arya A, Naema AF, Wong WF, Sethi G, Looi CY (2019) Signal transducer and activator of transcription (STATs) proteins in cancer and inflammation: functions and therapeutic implication. Front Oncol 9(FEB):48. https:\/\/doi.org\/10.3389\/fonc.2019.00048. Accessed 5 August 2020","DOI":"10.3389\/fonc.2019.00048"},{"key":"813_CR99","unstructured":"Longshaw AL, Fordyce EAF, Onions ST, King-Underwood J, Venable J (2016) INHIBITOR OF P38 MAP KINASE. US20150232450A1. https:\/\/patents.google.com\/patent\/US20150232450A1. Accessed 13 Aug 2020"},{"issue":"6","key":"813_CR100","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1111\/j.1471-4159.2005.03014.x","volume":"92","author":"S Lund","year":"2005","unstructured":"Lund S, Porzgen P, Mortensen AL, Hasseldam H, Bozyczko-Coyne D, Morath S, Hartung T, Bianchi M, Ghezzi P, Bsibsi M, Dijkstra S, Leist M (2005) Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. J Neurochem 92(6):1439\u20131451. https:\/\/doi.org\/10.1111\/j.1471-4159.2005.03014.x","journal-title":"J Neurochem"},{"issue":"5","key":"813_CR101","doi-asserted-by":"publisher","first-page":"569","DOI":"10.2174\/1381612053381927","volume":"11","author":"Y Ma","year":"2005","unstructured":"Ma Y, Pope R (2005) The role of macrophages in rheumatoid arthritis. Curr Pharm Des 11(5):569\u2013580. https:\/\/doi.org\/10.2174\/1381612053381927","journal-title":"Curr Pharm Des"},{"issue":"5\u20136","key":"813_CR102","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1177\/1759720X18776224","volume":"10","author":"CJ Malemud","year":"2018","unstructured":"Malemud CJ (2018) The role of the JAK\/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskel Dis 10(5\u20136):117\u2013127. https:\/\/doi.org\/10.1177\/1759720X18776224","journal-title":"Ther Adv Musculoskel Dis"},{"key":"813_CR103","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.atherosclerosis.2014.01.040","volume":"233","author":"W Martinet","year":"2014","unstructured":"Martinet W, De Loof H, De Meyer GRY (2014) MTOR inhibition: a promising strategy for stabilization of atherosclerotic plaques. Atherosclerosis 233:601\u2013607. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2014.01.040","journal-title":"Atherosclerosis"},{"issue":"9","key":"813_CR104","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1002\/j.1460-2075.1995.tb07189.x","volume":"14","author":"GA Martin","year":"1995","unstructured":"Martin GA, Bollag G, McCormick F, Abo A (1995) A novel serine kinase activated by rac1-CBC42Hs-dependent autophosphorylation is related to PAK65 and STE20. EMBO J 14(9):1970\u20131978. https:\/\/doi.org\/10.1002\/j.1460-2075.1995.tb07189.x","journal-title":"EMBO J"},{"key":"813_CR105","unstructured":"Menet CJM, Hodges AJ, Vater HD (2016) Compound useful for the treatment of degenerative and inflammatory diseases. US9241931B2. https:\/\/patents.google.com\/patent\/US9241931B2. Accessed 8 Aug 2020"},{"key":"813_CR106","unstructured":"Morris M, Pearson D (2020) What is the worldwide prevalence of asthma? Medscape https:\/\/www.medscape.com\/answers\/296301-7945\/what-is-the-worldwide-prevalence-of-asthma. Accessed 30 Nov 2020"},{"issue":"6","key":"813_CR107","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/978-94-015-97029_6","volume":"48","author":"O Morteau","year":"2000","unstructured":"Morteau O (2000) Prostaglandins and inflammation: the cyclooxygenase controversy. Arch Immunol Ther Exp 48(6):473\u2013480. https:\/\/doi.org\/10.1007\/978-94-015-97029_6","journal-title":"Arch Immunol Ther Exp"},{"issue":"19","key":"813_CR108","doi-asserted-by":"publisher","first-page":"10454","DOI":"10.1073\/pnas.180316397","volume":"97","author":"JS Mudgett","year":"2000","unstructured":"Mudgett JS, Ding J, Guh-Siesel L, Chartrain NA, Yang L, Gopal S, Shen MM (2000) Essential role for p38\u03b1 mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci USA 97(19):10454\u201310459. https:\/\/doi.org\/10.1073\/pnas.180316397","journal-title":"Proc Natl Acad Sci USA"},{"key":"813_CR109","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s12967-015-0627-5","volume":"13","author":"R Mukthavaram","year":"2015","unstructured":"Mukthavaram R, Ouyang X, Saklecha R, Jiang P, Nomura N, Pingle CS, Guo F, Makale M, Kesari S (2015) Effect of the JAK2\/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres. J Transl Med 13:269. https:\/\/doi.org\/10.1186\/s12967-015-0627-5","journal-title":"J Transl Med"},{"issue":"1\u20133","key":"813_CR110","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.ejphar.2010.02.037","volume":"635","author":"L Munoz","year":"2010","unstructured":"Munoz L, Ramsay EE, Manetsch M, Ge Q, Peifer C, Laufer S, Ammit AJ (2010) Novel p38 MAPK inhibitor ML3403 has potent anti-inflammatory activity in airway smooth muscle. Eur J Pharmacol 635(1\u20133):212\u2013218. https:\/\/doi.org\/10.1016\/j.ejphar.2010.02.037","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"813_CR111","doi-asserted-by":"publisher","first-page":"e54426","DOI":"10.1371\/journal.pone.0054426","volume":"8","author":"EM Mushaben","year":"2013","unstructured":"Mushaben EM, Brandt EB, Hershey GKK, Le Cras TD (2013) Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma. PLoS ONE 8(1):e54426. https:\/\/doi.org\/10.1371\/journal.pone.0054426","journal-title":"PLoS ONE"},{"key":"813_CR112","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.phrs.2018.12.004","volume":"141","author":"SM Nabavi","year":"2019","unstructured":"Nabavi SM, Ahmed T, Nawaz M (2019) Targeting STATs in neuroinflammation: the road less traveled! Pharmacol Res 141:73\u201384. https:\/\/doi.org\/10.1016\/j.phrs.2018.12.004","journal-title":"Pharmacol Res"},{"issue":"2","key":"813_CR113","doi-asserted-by":"publisher","first-page":"101","DOI":"10.26442\/00403660.2019.02.000155","volume":"91","author":"EL Nasonov","year":"2019","unstructured":"Nasonov EL, Abdulganieva DI, Fairushina IF (2019) The use of tofacitinib in the treatment of inflammatory bowel disease. Ter Arkh 91(2):101\u2013108. https:\/\/doi.org\/10.26442\/00403660.2019.02.000155","journal-title":"Ter Arkh"},{"issue":"5","key":"813_CR114","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nri3661","volume":"14","author":"MF Neurath","year":"2014","unstructured":"Neurath MF (2014) Cytokines in inflammatory bowel disease. Nat Rev Immunol 14(5):329\u2013342. https:\/\/doi.org\/10.1038\/nri3661","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"813_CR115","doi-asserted-by":"publisher","first-page":"a006049","DOI":"10.1101\/cshperspect.a006049","volume":"4","author":"K Newton","year":"2012","unstructured":"Newton K, Dixit VM (2012) Signaling in innate immunity and inflammation. Cold Spring Harbor Perspect Biol 4(3):a006049. https:\/\/doi.org\/10.1101\/cshperspect.a006049","journal-title":"Cold Spring Harbor Perspect Biol"},{"key":"813_CR116","unstructured":"ncbi.nlm.nih.gov (2020) STAT1\u00a0signal transducer and activator of transcription 1 [Homo sapiens\u00a0(human)]. https:\/\/www.ncbi.nlm.nih.gov\/gene\/6772. Accessed 8 Dec 2020"},{"issue":"3","key":"813_CR117","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/sj.onc.1201547","volume":"16","author":"RC O\u2019Hagan","year":"1998","unstructured":"O\u2019Hagan RC, Hassell JA (1998) The PEA3 Ets transcription factor is a downstream target of the HER2\/Neu receptor tyrosine kinase. Oncogene 16(3):301\u2013310. https:\/\/doi.org\/10.1038\/sj.onc.1201547","journal-title":"Oncogene"},{"issue":"18","key":"813_CR118","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1101\/gad.12.18.2874","volume":"12","author":"SM O\u2019Rourke","year":"1998","unstructured":"O\u2019Rourke SM, Herskowitz I (1998) The Hog1 MAPK prevents cross-talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12(18):2874\u20132886. https:\/\/doi.org\/10.1101\/gad.12.18.2874","journal-title":"Genes Dev"},{"issue":"1","key":"813_CR119","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s40268-015-0082-z","volume":"15","author":"B Pal","year":"2015","unstructured":"Pal B, Endisha H, Zhang Y, Kapoor M (2015) mTOR: a potential therapeutic target in osteoarthritis? Drugs in R and D 15(1):27\u201336. https:\/\/doi.org\/10.1007\/s40268-015-0082-z","journal-title":"Drugs in R and D"},{"key":"813_CR120","unstructured":"Paranjapan M, Viswanadha S, Babu G, Kumar S, Vakaranka VS (2019) Novel chromene kinase modulator. CN105801550B. https:\/\/patents.google.com\/patent\/CN105801550B. Accessed 13 Aug 2020"},{"issue":"6","key":"813_CR121","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/leu.2013.71","volume":"27","author":"A Pardanani","year":"2013","unstructured":"Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, Hogan WJ, Litzow MR, Leontovich A, Kowalski M, Tefferi A (2013) Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 27(6):1322\u20131327. https:\/\/doi.org\/10.1038\/leu.2013.71","journal-title":"Leukemia"},{"issue":"41","key":"813_CR122","doi-asserted-by":"publisher","first-page":"26722","DOI":"10.1074\/jbc.273.41.26722","volume":"273","author":"A Pedram","year":"1998","unstructured":"Pedram A, Razandi M, Levin ER (1998) Extracellular signal-regulated protein kinase\/jun kinase cross-talk underlies vascular endothelial cell growth factor-induced endothelial cell proliferation. J Biol Chem 273(41):26722\u201326728. https:\/\/doi.org\/10.1074\/jbc.273.41.26722","journal-title":"J Biol Chem"},{"issue":"3","key":"813_CR123","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nrrheum.2015.172","volume":"12","author":"A Perl","year":"2016","unstructured":"Perl A (2016) Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases. Nat Rev Rheumatol 12(3):169\u2013182. https:\/\/doi.org\/10.1038\/nrrheum.2015.172","journal-title":"Nat Rev Rheumatol"},{"issue":"5","key":"813_CR124","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.cell.2009.03.046","volume":"137","author":"TR Peterson","year":"2009","unstructured":"Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM (2009) DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137(5):873\u2013886. https:\/\/doi.org\/10.1016\/j.cell.2009.03.046","journal-title":"Cell"},{"issue":"13","key":"813_CR125","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1038\/sj.onc.1204184","volume":"20","author":"KL Pierce","year":"2001","unstructured":"Pierce KL, Luttrell LM, Lefkowitz RJ (2001) New mechanisms in heptahelical receptor signaling to mitogen-activated protein kinase cascades. Oncogene 20(13):1532\u20131539. https:\/\/doi.org\/10.1038\/sj.onc.1204184","journal-title":"Oncogene"},{"key":"813_CR126","doi-asserted-by":"publisher","unstructured":"Ptaschinski C, Lukacs NW (2018) Acute and chronic inflammation induces disease pathogenesis. Mol Pathol Mol Basis Human Dis 25\u201343. https:\/\/doi.org\/10.1016\/B978-0-12-802761-5.00002-X","DOI":"10.1016\/B978-0-12-802761-5.00002-X"},{"issue":"18","key":"813_CR127","doi-asserted-by":"publisher","first-page":"5144","DOI":"10.1523\/JNEUROSCI.4658-15.2016","volume":"36","author":"H Qin","year":"2016","unstructured":"Qin H, Buckley JA, Li X, Liu Y, Fox HT III, Meares PG, Yu H, Yan Z, Harms SA, Li Y, Standaert GD, Benveniste NE (2016) Inhibition of the JAK\/STAT pathway protects against \u03b1-synuclein-induced neuroinflammation and dopaminergic neurodegeneration. J Neurosci 36(18):5144\u20135159. https:\/\/doi.org\/10.1523\/JNEUROSCI.4658-15.2016","journal-title":"J Neurosci"},{"key":"813_CR128","doi-asserted-by":"publisher","first-page":"5662","DOI":"10.1038\/sj.onc.1203925","volume":"19","author":"S Rane","year":"2000","unstructured":"Rane S, Reddy E (2000) Janus kinases: components of multiple signaling pathways. Oncogene 19:5662\u20135679. https:\/\/doi.org\/10.1038\/sj.onc.1203925","journal-title":"Oncogene"},{"issue":"8","key":"813_CR129","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1242\/jcs.00963","volume":"117","author":"JS Rawlings","year":"2004","unstructured":"Rawlings JS, Rosler KM, Harrison DA (2004) The JAK\/STAT signaling pathway. J Cell Sci 117(8):1281\u20131283. https:\/\/doi.org\/10.1242\/jcs.00963","journal-title":"J Cell Sci"},{"issue":"1","key":"813_CR130","doi-asserted-by":"publisher","first-page":"259","DOI":"10.2174\/1874312901206010259","volume":"6","author":"KA Reedquist","year":"2012","unstructured":"Reedquist KA, Tak PP (2012) Signal transduction pathways in chronic inflammatory autoimmune disease: small GTPases. Open Rheumatol J 6(1):259\u2013272. https:\/\/doi.org\/10.2174\/1874312901206010259","journal-title":"Open Rheumatol J"},{"issue":"14","key":"813_CR131","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1021\/jm020057r","volume":"45","author":"J Regan","year":"2002","unstructured":"Regan J, Breitfelder S, Cirillo P (2002) Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate. J Med Chem 45(14):2994\u20133008. https:\/\/doi.org\/10.1021\/jm020057r","journal-title":"J Med Chem"},{"issue":"9","key":"813_CR132","doi-asserted-by":"publisher","first-page":"693","DOI":"10.3760\/cma.j.issn.1007-3418.2012.09.011","volume":"20","author":"F Ren","year":"2012","unstructured":"Ren F, Zhang HY, Piao ZF, Zheng SJ, Chen Y, Chen DX, Duan ZP (2012) Inhibition of glycogen synthase kinase 3b activity regulates Toll-like receptor 4-mediated liver inflammation. Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese J Hepatol 20(9):693\u2013697. https:\/\/doi.org\/10.3760\/cma.j.issn.1007-3418.2012.09.011","journal-title":"Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese J Hepatol"},{"key":"813_CR133","doi-asserted-by":"crossref","unstructured":"Renauld JC (2003) Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators. Nat Rev Immunol 3(8):667\u201376. https:\/\/www.nature.com\/articles\/nri1153. Accessed on 15 July 2020","DOI":"10.1038\/nri1153"},{"issue":"5","key":"813_CR134","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1021\/ml300049d","volume":"3","author":"KD Rice","year":"2012","unstructured":"Rice KD, Aay N, Anand NK et al (2012) Novel carboxamide-based allosteric MEK inhibitors: discovery and optimization efforts toward XL518 (GDC-0973). ACS Med Chem Lett 3(5):416\u2013421. https:\/\/doi.org\/10.1021\/ml300049d","journal-title":"ACS Med Chem Lett"},{"issue":"6","key":"813_CR135","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.3390\/molecules26061745","volume":"26","author":"R Romeo","year":"2021","unstructured":"Romeo R, Giofr\u00e8 VS, Chiacchio AM, Veltri L, Celesti C, Iannazzo D (2021) Synthesis and biological evaluation of 2,3,4-triaryl-1,2,4-oxadiazol-5-ones as p38 MAPK inhibitors. Molecules 26(6):1745. https:\/\/doi.org\/10.3390\/molecules26061745","journal-title":"Molecules"},{"issue":"8","key":"813_CR136","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/sj.leu.2402197","volume":"15","author":"PP Ruvolo","year":"2001","unstructured":"Ruvolo PP (2001) Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia 15(8):1153\u20131160. https:\/\/doi.org\/10.1038\/sj.leu.2402197","journal-title":"Leukemia"},{"issue":"6","key":"813_CR137","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41575-020-0273-0","volume":"17","author":"A Salas","year":"2020","unstructured":"Salas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S, Vetrano S, Vande Casteele N (2020) JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 17(6):323\u2013337. https:\/\/doi.org\/10.1038\/s41575-020-0273-0","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"6","key":"813_CR138","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","volume":"168","author":"RA Saxto","year":"2017","unstructured":"Saxto RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168(6):960\u2013976. https:\/\/doi.org\/10.1016\/j.cell.2017.02.004","journal-title":"Cell"},{"issue":"11","key":"813_CR139","doi-asserted-by":"publisher","first-page":"4648","DOI":"10.1158\/0008-5472.CAN-08-4455","volume":"69","author":"EM Schindler","year":"2009","unstructured":"Schindler EM, Hindes A, Gribben EL, Burns CJ, Yin Y, Lin MH, Owen RJ, Longmore GD, Kissling GE, Arthur JSC, Efimova T (2009) p38\u03b4 mitogen-activated protein kinase is essential for skin tumor development in mice. Can Res 69(11):4648\u20134655. https:\/\/doi.org\/10.1158\/0008-5472.CAN-08-4455","journal-title":"Can Res"},{"key":"813_CR140","doi-asserted-by":"publisher","unstructured":"Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O\u2019Shea JJ (2017) JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nature Rev Drug Discov 17(1)78. https:\/\/doi.org\/10.1038\/nrd.2017.267","DOI":"10.1038\/nrd.2017.267"},{"key":"813_CR141","doi-asserted-by":"publisher","unstructured":"Sever R, Brugge JS (2015) Signal transduction in cancer. Cold Spring Harbor Perspect Med 5(4). https:\/\/doi.org\/10.1101\/cshperspect.a006098","DOI":"10.1101\/cshperspect.a006098"},{"key":"813_CR142","doi-asserted-by":"publisher","unstructured":"Sgrignani J, Garofalo M, Matkovic M, Merulla J, Catapano CV, Cavalli A (2018) Structural biology of STAT3 and its implications for anticancer therapies development. Int J Mol Sci 19(6). https:\/\/doi.org\/10.3390\/ijms19061591","DOI":"10.3390\/ijms19061591"},{"key":"813_CR143","doi-asserted-by":"publisher","unstructured":"Shaheen M, Broxmeyer HE (2018) Cytokine\/receptor families and signal transduction. Hematol Basic Principles Pract 163\u2013175. https:\/\/doi.org\/10.1016\/B978-0-323-35762-3.00016-0","DOI":"10.1016\/B978-0-323-35762-3.00016-0"},{"key":"813_CR144","unstructured":"Sharfman WH (2018) Encorafenib and Binimetinib: a new benchmark in metastatic melanoma therapy. https:\/\/www.ascopost.com\/issues\/december-10-2018\/encorafenib-and-binimetinib\/. Accessed 13 Aug 2020"},{"issue":"2","key":"813_CR145","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1002\/jcp.27032","volume":"234","author":"G Shi","year":"2019","unstructured":"Shi G, Li D, Ren J, Li X, Wang T, Dou H, Hou Y (2019) mTOR inhibitor INK128 attenuates dextran sodium sulfate-induced colitis by promotion of MDSCs on Treg cell expansion. J Cell Physiol 234(2):1618\u20131629. https:\/\/doi.org\/10.1002\/jcp.27032","journal-title":"J Cell Physiol"},{"key":"813_CR146","unstructured":"Shokat KM, Fruman D, Ren P, Wilson TE, Li L,  Hsieh A,  Feldman M, Apsel B, Liu Y,  Rommel C, Chan K, Ruggero D, Pearce D,  Janes M (2017) MTOR modulators and uses thereof. US9629843B2. https:\/\/patents.google.com\/patent\/US9629843B2. Accessed 9 Aug 2020"},{"key":"813_CR147","doi-asserted-by":"publisher","unstructured":"Skalkoyannis B, Kanamarlapudi V (2018) STAT6. Encycl Signal Mol 5175\u20135182. https:\/\/doi.org\/10.1007\/978-3-319-67199-4_101988","DOI":"10.1007\/978-3-319-67199-4_101988"},{"issue":"5","key":"813_CR148","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nchembio.2056","volume":"12","author":"GA Smith","year":"2016","unstructured":"Smith GA, Uchida K, Weiss A, Taunton J (2016) Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling. Nat Chem Biol 12(5):373\u2013379. https:\/\/doi.org\/10.1038\/nchembio.2056","journal-title":"Nat Chem Biol"},{"issue":"5164","key":"813_CR149","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1126\/science.7811320","volume":"264","author":"D Stokoe","year":"1994","unstructured":"Stokoe D, Macdonald SG, Cadwallader K, Symons M, Hancock JF (1994) Activation of Raf as a result of recruitment to the plasma membrane. Science 264(5164):1463\u20131467. https:\/\/doi.org\/10.1126\/science.7811320","journal-title":"Science"},{"issue":"1","key":"813_CR150","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fnmol.2014.00028","volume":"7","author":"N Takei","year":"2014","unstructured":"Takei N, Nawa H (2014) mTOR signaling and its roles in normal and abnormal brain development. Front Mol Neurosci 7(1):28. https:\/\/doi.org\/10.3389\/fnmol.2014.00028","journal-title":"Front Mol Neurosci"},{"key":"813_CR151","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1146\/annurev.immunol.23.021704.115816","volume":"23","author":"PR Taylor","year":"2005","unstructured":"Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S (2005) Macrophage receptors and immune recognition. Annu Rev Immunol 23:901\u2013944. https:\/\/doi.org\/10.1146\/annurev.immunol.23.021704.115816","journal-title":"Annu Rev Immunol"},{"issue":"11","key":"813_CR152","doi-asserted-by":"publisher","first-page":"e1217","DOI":"10.1371\/journal.pone.0001217","volume":"2","author":"K Thedieck","year":"2007","unstructured":"Thedieck K, Polak P, Kim ML, Molle KD, Cohen A, Jen\u00f6 P, Arrieumerlou C, Hall MN (2007) PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis. PLoS ONE 2(11):e1217. https:\/\/doi.org\/10.1371\/journal.pone.0001217","journal-title":"PLoS ONE"},{"issue":"5467","key":"813_CR153","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1126\/science.288.5467.870","volume":"288","author":"C Tournier","year":"2000","unstructured":"Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA, Davis RJ (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288(5467):870\u2013874. https:\/\/doi.org\/10.1126\/science.288.5467.870","journal-title":"Science"},{"key":"813_CR154","doi-asserted-by":"publisher","unstructured":"Tramutola A, Lanzillotta C and Di Domenico F (2017) Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies. Expert Rev Neurother 33\u201345. https:\/\/doi.org\/10.1080\/14737175.2017.1244482","DOI":"10.1080\/14737175.2017.1244482"},{"issue":"4","key":"813_CR155","doi-asserted-by":"publisher","first-page":"405","DOI":"10.4155\/fmc.16.4","volume":"8","author":"K Vale","year":"2016","unstructured":"Vale K (2016) Targeting the JAK-STAT pathway in the treatment of \u201cTh2-high\u201d severe asthma. Future Med Chem 8(4):405\u2013419. https:\/\/doi.org\/10.4155\/fmc.16.4","journal-title":"Future Med Chem"},{"key":"813_CR156","unstructured":"Vasios G (2008) JAK\/STAT pathway inhibitors and the use thereof for the treatment of osteoarthritis. EP1875900A2. https:\/\/patents.google.com\/patent\/EP1875900A2. Accessed 9 August 2020"},{"issue":"2","key":"813_CR157","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.diabres.2015.09.014","volume":"110","author":"B Verg\u00e8s","year":"2015","unstructured":"Verg\u00e8s B, Cariou B (2015) MTOR inhibitors and diabetes. Diabetes Res Clin Pract 110(2):101\u2013108. https:\/\/doi.org\/10.1016\/j.diabres.2015.09.014","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"813_CR158","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1111\/bcp.13078","volume":"82","author":"O von Richter","year":"2016","unstructured":"von Richter O, Massimini G, Scheible H, Udvaros I, Johne A (2016) Pimasertib, a selective oral MEK1\/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients. Br J Clin Pharmacol 82(6):1498\u20131508. https:\/\/doi.org\/10.1111\/bcp.13078","journal-title":"Br J Clin Pharmacol"},{"issue":"5266","key":"813_CR159","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1126\/science.272.5266.1347","volume":"272","author":"XZ Wang","year":"1996","unstructured":"Wang XZ, Ron D (1996) Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase. Science 272(5266):1347\u20131349. https:\/\/doi.org\/10.1126\/science.272.5266.1347","journal-title":"Science"},{"issue":"1","key":"813_CR160","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4161\/jkst.19418","volume":"1","author":"Y Wang","year":"2012","unstructured":"Wang Y, Levy DE (2012) Comparative evolutionary genomics of the STAT family of transcription factors. JAK-STAT 1(1):23\u201336. https:\/\/doi.org\/10.4161\/jkst.19418","journal-title":"JAK-STAT"},{"issue":"1","key":"813_CR161","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/sj.cr.7290105","volume":"12","author":"Z Wei","year":"2002","unstructured":"Wei Z, Liu HT (2002) MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 12(1):9\u201318. https:\/\/doi.org\/10.1038\/sj.cr.7290105","journal-title":"Cell Res"},{"key":"813_CR22","unstructured":"WHO|Chronic Rheumatic Conditions (2016) WHO. http:\/\/www.who.int\/chp\/topics\/rheumatic\/en\/. Accessed 30 Dec 2020"},{"issue":"1","key":"813_CR162","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1152\/physrev.1999.79.1.143","volume":"79","author":"C Widmann","year":"1999","unstructured":"Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79(1):143\u2013180. https:\/\/doi.org\/10.1152\/physrev.1999.79.1.143","journal-title":"Physiol Rev"},{"key":"813_CR163","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3418975","author":"RSY Wong","year":"2019","unstructured":"Wong RSY (2019) Role of nonsteroidal anti-inflammatory drugs (NSAIDs) in cancer prevention and cancer promotion. Adv Pharmacol Sci. https:\/\/doi.org\/10.1155\/2019\/3418975","journal-title":"Adv Pharmacol Sci"},{"issue":"4","key":"813_CR164","doi-asserted-by":"publisher","first-page":"255","DOI":"10.7497\/j.issn.2095-3941.2014.04.004","volume":"11","author":"SH Wu","year":"2014","unstructured":"Wu SH, Bi JF, Cloughesy T, Cavenee WK, Mischel PS (2014) Emerging function of mTORC2 as a core regulator in glioblastoma: metabolic reprogramming and drug resistance. Cancer Biol Med 11(4):255\u2013263. https:\/\/doi.org\/10.7497\/j.issn.2095-3941.2014.04.004","journal-title":"Cancer Biol Med"},{"issue":"12","key":"813_CR165","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1186\/gb-2004-5-12-253","volume":"5","author":"K Yamaoka","year":"2004","unstructured":"Yamaoka K, Saharinen P, Pesu M, Holt VET, Silvennoinen O, O\u2019Shea JJ (2004) The Janus kinases (Jaks). Genome Biol 5(12):253. https:\/\/doi.org\/10.1186\/gb-2004-5-12-253","journal-title":"Genome Biol"},{"key":"813_CR166","doi-asserted-by":"publisher","unstructured":"Yang WS, Park YC, Kim JH, Kim HR, Yu T, Byeon SE, Unsworth LD, Lee J, Cho JY (2012) Nanostructured, self-assembling peptide K5 blocks TNF- and PGE 2 production by suppression of the AP-1\/p38 pathway. Mediators Inflam https:\/\/doi.org\/10.1155\/2012\/489810","DOI":"10.1155\/2012\/489810"},{"key":"813_CR167","doi-asserted-by":"publisher","unstructured":"Yang Y, Kim SC, Yu T, Yi YS, Rhee MH, Sung GH, Yoo BC, Cho JY (2014) Functional roles of p38 mitogen-activated protein kinase in macrophage-mediated inflammatory responses. Mediators Inflam. https:\/\/doi.org\/10.1155\/2014\/352371","DOI":"10.1155\/2014\/352371"},{"issue":"10","key":"813_CR168","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1161\/01.RES.0000268411.49545.9c","volume":"100","author":"M Yano","year":"2007","unstructured":"Yano M, Matsumura T, Senokuchi T, Ishii N, Murata Y, Taketa K, Motoshima H, Taguchi T, Sonoda K, Kukidome D, Takuwa Y, Kawada T, Brownlee M, Nishikawa T, Araki E (2007) Statins activate peroxisome proliferator-activated receptor \u03b3 through extracellular signal-regulated kinase 1\/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res 100(10):1442\u20131451. https:\/\/doi.org\/10.1161\/01.RES.0000268411.49545.9c","journal-title":"Circ Res"},{"key":"813_CR169","unstructured":"Yasir M, Sonthalia S (2019) Corticosteroid adverse effects. StatPearls Publishing. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30285357. Accessed 5 August 2020"},{"issue":"11","key":"813_CR170","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/nrc2734","volume":"9","author":"H Yu","year":"2009","unstructured":"Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9(11):798\u2013809. https:\/\/doi.org\/10.1038\/nrc2734","journal-title":"Nat Rev Cancer"},{"key":"813_CR171","doi-asserted-by":"publisher","unstructured":"Yu T, Yi YS, Yang Y, Oh J, Jeong D, Cho JY (2012) The pivotal role of TBK1 in inflammatory responses mediated by macrophages. Mediators Inflam. https:\/\/doi.org\/10.1155\/2012\/979105. Accessed 15 July 2020","DOI":"10.1155\/2012\/979105"},{"issue":"1","key":"813_CR172","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-04826-y","volume":"7","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Jing Y, Qiao J, Luan B, Wang X, Wang L, Song Z (2017) Activation of the mTOR signaling pathway is required for asthma onset. Sci Rep 7(1):1\u201313. https:\/\/doi.org\/10.1038\/s41598-017-04826-y","journal-title":"Sci Rep"},{"issue":"4","key":"813_CR173","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.4049\/jimmunol.178.4.2163","volume":"178","author":"CSL ZhengY","year":"2007","unstructured":"ZhengY CSL, Lutz MA, Allen AN, Kole TP, Zarek PE, Powell JD (2007) A role for mammalian target of rapamycin in regulating T cell activation versus anergy. J Immunol 178(4):2163\u20132170. https:\/\/doi.org\/10.4049\/jimmunol.178.4.2163","journal-title":"J Immunol"},{"issue":"12","key":"813_CR174","doi-asserted-by":"publisher","first-page":"4371","DOI":"10.1128\/mcb.20.12.4371-4380.2000","volume":"20","author":"YJ Zhou","year":"2000","unstructured":"Zhou YJ, Magnuson KS, Cheng TP, Gadina M, Frucht DM, Galon J, Candotti F, Geahlen RL, Changelian PS, O\u2019Shea JJ (2000) Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of Syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation. Mol Cell Biol 20(12):4371\u20134380. https:\/\/doi.org\/10.1128\/mcb.20.12.4371-4380.2000","journal-title":"Mol Cell Biol"},{"issue":"5","key":"813_CR175","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/S1097-2765(01)00398-7","volume":"8","author":"YJ Zhou","year":"2001","unstructured":"Zhou YJ, Chen M, Cusack NA, Kimmel LH, Magnuson KS, Boyd JG, Lin W, Roberts JL, Lengi A, Buckley RH, Geahlen RL, Candotti F, Gadina M, Changelian PS, O\u2019Shea JJ (2001) Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. Mol Cell 8(5):959\u2013969. https:\/\/doi.org\/10.1016\/S1097-2765(01)00398-7","journal-title":"Mol Cell"},{"key":"813_CR176","doi-asserted-by":"publisher","unstructured":"Zhu Z, Yang C, Iyaswamy A, Krishnamoorthi S, Sreenivasmurthy SG, Liu J, Wang Z, Tong BCK, Song J, Lu J, Cheung KH, Li M (2019) Balancing mTOR signaling and autophagy in the treatment of Parkinson\u2019s disease. Int J Mol Sci MDPI AG. https:\/\/doi.org\/10.3390\/ijms20030728. Accessed 1 August 2020","DOI":"10.3390\/ijms20030728"},{"issue":"1","key":"813_CR177","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13578-020-00396-1","volume":"10","author":"Z Zou","year":"2020","unstructured":"Zou Z, Tao T, Li H, Zhu X (2020) MTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci 10(1):31. https:\/\/doi.org\/10.1186\/s13578-020-00396-1","journal-title":"Cell Biosci"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-021-00813-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-021-00813-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-021-00813-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T10:14:38Z","timestamp":1624616078000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-021-00813-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":177,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["813"],"URL":"https:\/\/doi.org\/10.1007\/s10787-021-00813-y","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"assertion":[{"value":"20 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no competing interests to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable since it is a review article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}