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Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK).
Watterson, Scott H; Liu, Qingjie; Beaudoin Bertrand, Myra; Batt, Douglas G; Li, Ling; Pattoli, Mark A; Skala, Stacey; Cheng, Lihong; Obermeier, Mary T; Moore, Robin; Yang, Zheng; Vickery, Rodney; Elzinga, Paul A; Discenza, Lorell; D'Arienzo, Celia; Gillooly, Kathleen M; Taylor, Tracy L; Pulicicchio, Claudine; Zhang, Yifan; Heimrich, Elizabeth; McIntyre, Kim W; Ruan, Qian; Westhouse, Richard A; Catlett, Ian M; Zheng, Naiyu; Chaudhry, Charu; Dai, Jun; Galella, Michael A; Tebben, Andrew J; Pokross, Matt; Li, Jianqing; Zhao, Rulin; Smith, Daniel; Rampulla, Richard; Allentoff, Alban; Wallace, Michael A; Mathur, Arvind; Salter-Cid, Luisa; Macor, John E; Carter, Percy H; Fura, Aberra; Burke, James R; Tino, Joseph A.
Afiliação
  • Watterson SH; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Liu Q; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Beaudoin Bertrand M; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Batt DG; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Li L; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Pattoli MA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Skala S; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Cheng L; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Obermeier MT; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Moore R; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Yang Z; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Vickery R; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Elzinga PA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Discenza L; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • D'Arienzo C; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Gillooly KM; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Taylor TL; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Pulicicchio C; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Zhang Y; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Heimrich E; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • McIntyre KW; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Ruan Q; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Westhouse RA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Catlett IM; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Zheng N; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Chaudhry C; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Dai J; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Galella MA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Tebben AJ; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Pokross M; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Li J; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Zhao R; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Smith D; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Rampulla R; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Allentoff A; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Wallace MA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Mathur A; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Salter-Cid L; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Macor JE; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Carter PH; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Fura A; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Burke JR; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
  • Tino JA; Bristol-Myers Squibb Research and Development , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
J Med Chem ; 62(7): 3228-3250, 2019 04 11.
Article em En | MEDLINE | ID: mdl-30893553
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperidinas / Inibidores de Proteínas Quinases / Descoberta de Drogas / Tirosina Quinase da Agamaglobulinemia / Indóis Limite: Animals / Humans Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperidinas / Inibidores de Proteínas Quinases / Descoberta de Drogas / Tirosina Quinase da Agamaglobulinemia / Indóis Limite: Animals / Humans Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos