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Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ.
Somoza, John R; Koditek, David; Villaseñor, Armando G; Novikov, Nikolai; Wong, Melanie H; Liclican, Albert; Xing, Weimei; Lagpacan, Leanna; Wang, Ruth; Schultz, Brian E; Papalia, Giuseppe A; Samuel, Dharmaraj; Lad, Latesh; McGrath, Mary E.
Afiliação
  • Somoza JR; From the Departments of Structural Chemistry and john.somoza@gilead.com.
  • Koditek D; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Villaseñor AG; From the Departments of Structural Chemistry and.
  • Novikov N; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Wong MH; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Liclican A; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Xing W; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Lagpacan L; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Wang R; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Schultz BE; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Papalia GA; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Samuel D; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • Lad L; Biology, Gilead Sciences, Inc., Foster City, California 94404.
  • McGrath ME; From the Departments of Structural Chemistry and.
J Biol Chem ; 290(13): 8439-46, 2015 Mar 27.
Article em En | MEDLINE | ID: mdl-25631052
Idelalisib (also known as GS-1101, CAL-101, IC489666, and Zydelig) is a PI3Kδ inhibitor that has recently been approved for the treatment of several hematological malignancies. Given its use in human diseases, we needed a clear picture of how idelalisib binds to and inhibits PI3Kδ. Our data show that idelalisib is a potent and selective inhibitor of the kinase activity of PI3Kδ. A kinetic characterization clearly demonstrated ATP-competitive inhibition, and several additional biochemical and biophysical assays showed that the compound binds reversibly and noncovalently to the kinase. A crystal structure of idelalisib bound to the p110δ subunit of PI3Kδ furthers our understanding of the binding interactions that confer the potency and selectivity of idelalisib.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Purinas / Fosfatidilinositol 3-Quinases / Quinazolinonas Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Purinas / Fosfatidilinositol 3-Quinases / Quinazolinonas Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2015 Tipo de documento: Article