Download MendeleyStructural, Biochemical, and Biophysical Characterization of Idelalisib Binding to Phosphoinositide 3-Kinase delta.
Somoza, J.R., Koditek, D., Villasenor, A.G., Novikov, N., Wong, M.H., Liclican, A., Xing, W., Lagpacan, L., Wang, R., Schultz, B.E., Papalia, G.A., Samuel, D., Lad, L., McGrath, M.E.(2015) J Biol Chem 290: 8439-8446
- PubMed: 25631052
- DOI: https://doi.org/10.1074/jbc.M114.634683
- Primary Citation of Related Structures:
4XE0 - PubMed Abstract:
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.
Organizational Affiliation:
From the Departments of Structural Chemistry and john.somoza@gilead.com.
