{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:30:37Z","timestamp":1784251837692,"version":"3.55.0"},"reference-count":106,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti\u2010citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B\u2010lineage cells by preventing BCR activation, FC\u2010receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in\u00a0vitro and in\u00a0vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune\u2010mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.<\/jats:p>","DOI":"10.1111\/cbdd.14582","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T02:11:40Z","timestamp":1721182300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic potential and recent progression of <scp>BTK<\/scp> inhibitors against rheumatoid arthritis"],"prefix":"10.1111","volume":"104","author":[{"given":"Swati","family":"Paliwal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry DPSRU  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-5422","authenticated-orcid":false,"given":"Sandhya","family":"Bawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry SPER, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishtha","family":"Shalmali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry SPER, Jamia Hamdard  New Delhi India"},{"name":"Dr. K. N. Modi Institute of Pharmaceutical Education and Research  Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv K.","family":"Tonk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry DPSRU  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"e_1_2_19_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.668162"},{"key":"e_1_2_19_3_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.190434"},{"key":"e_1_2_19_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-6-59"},{"key":"e_1_2_19_5_1","first-page":"199","article-title":"A brief review of pathophysiology and management of different types of arthritis","volume":"12","author":"Ali S.","year":"2022","journal-title":"European Chemical Bulletin"},{"key":"e_1_2_19_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1086999"},{"issue":"19","key":"e_1_2_19_7_1","first-page":"4322","article-title":"Macrophage activation syndrome as a complication of juvenile rheumatoid arthritis","volume":"21","author":"An Q.","year":"2017","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_19_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntw030"},{"key":"e_1_2_19_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2019.100201"},{"key":"e_1_2_19_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S288550"},{"key":"e_1_2_19_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.242909"},{"key":"e_1_2_19_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102741"},{"key":"e_1_2_19_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780198831433.003.0005"},{"key":"e_1_2_19_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_19_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147641"},{"key":"e_1_2_19_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000493390"},{"key":"e_1_2_19_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00794"},{"key":"e_1_2_19_18_1","volume-title":"Rheumatoid arthritis","author":"Chauhan K.","year":"2023"},{"key":"e_1_2_19_19_1","unstructured":"ClinicalTrials.govA Study to Evaluate the Long\u2010Term Safety and Efficacy of GDC\u20100853 in Participants With Moderate to Severe Rheumatoid Arthritis Enrolled in Study GA29350. Identifier: NCT02983227."},{"key":"e_1_2_19_20_1","unstructured":"ClinicalTrials.govStudy to Evaluate the Safety and Tolerability of Tirabrutinib (ONO\/GS\u20104059) Given as Monotherapy in Participants With Relapsed\/Refractory NHL and CLL. NCT01659255."},{"key":"e_1_2_19_21_1","unstructured":"ClinicalTrials.govEfficacy and Safety Study of BMS\u2010986142 in Patients With Moderate to Severe Rheumatoid Arthritis. NCT02638948."},{"key":"e_1_2_19_22_1","unstructured":"ClinicalTrials.govPhase IIb Study of Evobrutinib in Subjects With Rheumatoid Arthritis (NCT03233230)."},{"key":"e_1_2_19_23_1","unstructured":"ClinicalTrials.govSafety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis (NCT02784106)."},{"key":"e_1_2_19_24_1","unstructured":"ClinicalTrials.govACP\u2010196 versus Placebo in Subjects With Rheumatoid Arthritis on Background Methotrexate. Identifier: NCT02387762."},{"key":"e_1_2_19_25_1","unstructured":"ClinicalTrials.govSafety and Efficacy Study of GDC\u20100853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA). Identifier: NCT02833350."},{"key":"e_1_2_19_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41275"},{"key":"e_1_2_19_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.053"},{"key":"e_1_2_19_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01712"},{"key":"e_1_2_19_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.07.010"},{"key":"e_1_2_19_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30155"},{"key":"e_1_2_19_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4555"},{"key":"e_1_2_19_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01318-8"},{"key":"e_1_2_19_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.481"},{"key":"e_1_2_19_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-26660-2_2"},{"key":"e_1_2_19_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.52"},{"key":"e_1_2_19_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00597"},{"key":"e_1_2_19_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2669"},{"issue":"7","key":"e_1_2_19_38_1","first-page":"S128","article-title":"Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A synopsis","volume":"20","author":"Gibofsky A.","year":"2014","journal-title":"The American Journal of Managed Care"},{"key":"e_1_2_19_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181782"},{"key":"e_1_2_19_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051456"},{"key":"e_1_2_19_41_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde-2020-0029"},{"key":"e_1_2_19_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0435"},{"key":"e_1_2_19_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010018\u20100016\u20109"},{"key":"e_1_2_19_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.2908.2908"},{"key":"e_1_2_19_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800583"},{"key":"e_1_2_19_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2005.04.040"},{"key":"e_1_2_19_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24328"},{"key":"e_1_2_19_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1056"},{"key":"e_1_2_19_49_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.086918"},{"key":"e_1_2_19_50_1","doi-asserted-by":"crossref","unstructured":"Isenberg D. Furie R. Jones N. S. Guibord P. Galanter J. Lee C. &Tuckwell K.(2020).OP0233 efficacy safety and pharmacodynamic effects of the bruton's tyrosine kinase inhibitor fenebrutinib (GDC\u20100853) in moderate to severe systemic lupus erythematosus in a phase 2 controlled study.","DOI":"10.1136\/annrheumdis-2020-eular.2949"},{"key":"e_1_2_19_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.19400"},{"key":"e_1_2_19_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020905"},{"key":"e_1_2_19_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u2010203323"},{"key":"e_1_2_19_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01147"},{"key":"e_1_2_19_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1402-1"},{"key":"e_1_2_19_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010012\u20108346\u20107"},{"key":"e_1_2_19_57_1","doi-asserted-by":"publisher","DOI":"10.19082\/6500"},{"key":"e_1_2_19_58_1","first-page":"261","article-title":"THU0185 safety, pharmacokinetics and proof\u2010of\u2010mechanism of an oral Bruton's tyrosine kinase inhibitor HM71224 in healthy adult volunteers","volume":"74","author":"Lee J.","year":"2015","journal-title":"Annals of the Rheumatic Diseases"},{"key":"e_1_2_19_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-017-2226-2"},{"key":"e_1_2_19_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041244"},{"key":"e_1_2_19_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.923"},{"key":"e_1_2_19_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.03.062"},{"key":"e_1_2_19_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040880"},{"key":"e_1_2_19_64_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.181545"},{"issue":"15","key":"e_1_2_19_65_1","first-page":"6260","article-title":"Discovery of potent and selective Bruton's tyrosine kinase (BTK) inhibitors: Importance of the hinge binding motif and the amine tail","volume":"56","author":"Liu S.","year":"2013","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_19_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/v4123701"},{"key":"e_1_2_19_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500305p"},{"key":"e_1_2_19_68_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666180316121951"},{"key":"e_1_2_19_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00702"},{"key":"e_1_2_19_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38047"},{"key":"e_1_2_19_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.11.012"},{"key":"e_1_2_19_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27425"},{"key":"e_1_2_19_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01592-0"},{"key":"e_1_2_19_74_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2016.1182499"},{"key":"e_1_2_19_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39657"},{"key":"e_1_2_19_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2019.101477"},{"key":"e_1_2_19_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0988-z"},{"key":"e_1_2_19_78_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102018\u2010213625"},{"key":"e_1_2_19_79_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4704"},{"key":"e_1_2_19_80_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.662223"},{"key":"e_1_2_19_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11102807"},{"key":"e_1_2_19_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.689698"},{"key":"e_1_2_19_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9103109"},{"key":"e_1_2_19_84_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131241"},{"key":"e_1_2_19_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-019-00182-7"},{"key":"e_1_2_19_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.22980"},{"key":"e_1_2_19_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13673"},{"key":"e_1_2_19_88_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.081306"},{"issue":"7","key":"e_1_2_19_89_1","first-page":"1638","article-title":"Genetic association between rheumatoid arthritis and estrogen receptor microsatellite polymorphism","volume":"27","author":"Takagi H.","year":"2000","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_19_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26237411"},{"key":"e_1_2_19_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-019-04699-8"},{"key":"e_1_2_19_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2015.09.001"},{"key":"e_1_2_19_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2018.10.005"},{"key":"e_1_2_19_94_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2022.2106970"},{"key":"e_1_2_19_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.237"},{"key":"e_1_2_19_96_1","first-page":"111","article-title":"Efficacy and safety of evobrutinib (M2951) in adult patients with systemic lupus erythematosus who received standard of care therapy: A phase II, randomized, double\u2010blind, placebo\u2010controlled dose ranging study","volume":"72","author":"Wallace D. J.","year":"2020","journal-title":"Arthritis and Rheumatology"},{"key":"e_1_2_19_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytol.2019.09.011"},{"key":"e_1_2_19_98_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.750753"},{"key":"e_1_2_19_99_1","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.19320"},{"key":"e_1_2_19_100_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0250-9"},{"key":"e_1_2_19_101_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051127"},{"key":"e_1_2_19_102_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.187740"},{"key":"e_1_2_19_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15061194"},{"key":"e_1_2_19_104_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7100161"},{"key":"e_1_2_19_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201700369"},{"key":"e_1_2_19_106_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57030266"},{"key":"e_1_2_19_107_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41061-019-0252-5"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T07:11:53Z","timestamp":1722237113000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":106,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/cbdd.14582"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14582","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2024-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14582"}}