| Literature DB >> 30893553 |
Scott H Watterson1, Qingjie Liu1, Myra Beaudoin Bertrand1, Douglas G Batt1, Ling Li1, Mark A Pattoli1, Stacey Skala1, Lihong Cheng1, Mary T Obermeier1, Robin Moore1, Zheng Yang1, Rodney Vickery1, Paul A Elzinga1, Lorell Discenza1, Celia D'Arienzo1, Kathleen M Gillooly1, Tracy L Taylor1, Claudine Pulicicchio1, Yifan Zhang1, Elizabeth Heimrich1, Kim W McIntyre1, Qian Ruan1, Richard A Westhouse1, Ian M Catlett1, Naiyu Zheng1, Charu Chaudhry1, Jun Dai1, Michael A Galella1, Andrew J Tebben1, Matt Pokross1, Jianqing Li1, Rulin Zhao1, Daniel Smith1, Richard Rampulla1, Alban Allentoff1, Michael A Wallace1, Arvind Mathur1, Luisa Salter-Cid1, John E Macor1, Percy H Carter1, Aberra Fura1, James R Burke1, Joseph A Tino1.
Abstract
Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.Entities:
Year: 2019 PMID： 30893553 DOI： 10.1021/acs.jmedchem.9b00167
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446