Unknown

Dataset Information

0

Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase ?.

ABSTRACT: Idelalisib (also known as GS-1101, CAL-101, IC489666, and Zydelig) is a PI3K? 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 PI3K?. Our data show that idelalisib is a potent and selective inhibitor of the kinase activity of PI3K?. 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 p110? subunit of PI3K? furthers our understanding of the binding interactions that confer the potency and selectivity of idelalisib.

SUBMITTER: Somoza JR 

PROVIDER: S-EPMC4375495 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ.

Somoza John R JR   Koditek David D   Villaseñor Armando G AG   Novikov Nikolai N   Wong Melanie H MH   Liclican Albert A   Xing Weimei W   Lagpacan Leanna L   Wang Ruth R   Schultz Brian E BE   Papalia Giuseppe A GA   Samuel Dharmaraj D   Lad Latesh L   McGrath Mary E ME  

The Journal of biological chemistry 20150128 13

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 bio  ...[more]

Similar Datasets

Unknown Structural and biophysical characterization of the nucleosome-binding PZP domain.
| S-EPMC8082262 | biostudies-literature
Unknown Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis.
| S-EPMC7310628 | biostudies-literature
Unknown Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis.
| S-EPMC7771249 | biostudies-literature
Unknown Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis
| EMPIAR-10433 | biostudies-other
Unknown Biochemical and biophysical characterization of four EphB kinase domains reveals contrasting thermodynamic, kinetic and inhibition profiles.
| S-EPMC3673036 | biostudies-literature
Unknown Structural and biochemical characterization of compounds inhibiting Mycobacterium tuberculosis pantothenate kinase.
| S-EPMC3689968 | biostudies-literature
Unknown Molecular cloning and biochemical characterization of a Drosophila phosphatidylinositol-specific phosphoinositide 3-kinase.
| S-EPMC1218144 | biostudies-other
Unknown Biochemical and biophysical characterization of natural polyreactivity in antibodies.
| S-EPMC10858392 | biostudies-literature
Unknown Biochemical and biophysical characterization of cytokine-like protein 1 (CYTL1).
| S-EPMC5507608 | biostudies-literature
Unknown Biochemical and biophysical characterization of Leishmania donovani gamma-glutamylcysteine synthetase.
| S-EPMC5613772 | biostudies-literature