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ZYBT1 is a potent, irreversible, specific BTK inhibitor that inhibits the ibrutinib\u2010resistant C481S BTK with nanomolar potency. ZYBT1 is found to be a promising molecule to treat both cancer and RA. In the present report we profiled the molecule for in\u2010vitro, in\u2010vivo activity, and pharmacokinetic properties. ZYBT1 inhibits BTK and C481S BTK with an IC<jats:sub>50<\/jats:sub> of 1\u00a0nmol\/L and 14\u00a0nmol\/L, respectively, inhibits the growth of various leukemic cell lines with IC<jats:sub>50<\/jats:sub> of 1\u00a0nmol\/L to 15\u00a0\u03bcmol\/L, blocks the phosphorylation of BTK and PLC\u03b32, and inhibits secretion of TNF\u2010\u03b1, IL\u20108 and IL\u20106. It has favorable pharmacokinetic properties suitable for using as an oral anti\u2010cancer and anti\u2010arthritic drug. In accordance with the in\u2010vitro properties, it demonstrated robust efficacy in murine models of collagen\u2010induced arthritis (CIA) and streptococcal cell wall (SCW) induced arthritis. In both models, ZYBT1 alone could suppress the progression of the diseases. It also reduced the growth of TMD8 xenograft tumor. The results suggested that ZYBT1 has high potential for treating RA, and cancer.<\/jats:p>","DOI":"10.1002\/prp2.565","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T13:25:16Z","timestamp":1597325116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["ZYBT1, a potent, irreversible Bruton\u2019s Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-2854","authenticated-orcid":false,"given":"Krishnarup","family":"Ghoshdastidar","sequence":"first","affiliation":[{"name":"Department of Cell Biology Zydus Research Center Ahmedabad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoshang","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Zydus Research Center 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