Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ
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. Here, 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. Lastly, 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.
- Authors:
-
- Gilead Sciences, Inc., Foster City, CA (United States)
- Publication Date:
- Research Org.:
- Univ. of California, Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1347695
- Alternate Identifier(s):
- OSTI ID: 1347696
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biological Chemistry
- Additional Journal Information:
- Journal Volume: 290; Journal Issue: 13; Journal ID: ISSN 0021-9258
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; CAL-101; enzyme kinetics; enzyme mechanism; enzyme purification; GS-1101; PI3K; PI3Kδ; phosphatidylinositide 3-kinase (PI 3-kinase); surface plasmon resonance (SPR); zydelig
Citation Formats
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, and McGrath, Mary E. Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ. United States: N. p., 2015.
Web. doi:10.1074/jbc.m114.634683.
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. Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ. United States. https://doi.org/10.1074/jbc.m114.634683
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, and McGrath, Mary E. Wed .
"Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ". United States. https://doi.org/10.1074/jbc.m114.634683. https://www.osti.gov/servlets/purl/1347695.
@article{osti_1347695,
title = {Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase δ},
author = {Somoza, John R. and Koditek, David and Villaseñor, Armando G. and Novikov, Nikolai and Wong, Melanie H. and Liclican, Albert and Xing, Weimei and Lagpacan, Leanna and Wang, Ruth and Schultz, Brian E. and Papalia, Giuseppe A. and Samuel, Dharmaraj and Lad, Latesh and McGrath, Mary E.},
abstractNote = {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. Here, 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. Lastly, 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.},
doi = {10.1074/jbc.m114.634683},
journal = {Journal of Biological Chemistry},
number = 13,
volume = 290,
place = {United States},
year = {Wed Jan 28 00:00:00 EST 2015},
month = {Wed Jan 28 00:00:00 EST 2015}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 112 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
journal, January 2011
- Lannutti, Brian J.; Meadows, Sarah A.; Herman, Sarah E. M.
- Blood, Vol. 117, Issue 2
PI3K p110δ regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
journal, March 2010
- Soond, Dalya R.; Bjørgo, Elisa; Moltu, Kristine
- Blood, Vol. 115, Issue 11
Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia
journal, May 2014
- Brown, Jennifer R.; Byrd, John C.; Coutre, Steven E.
- Blood, Vol. 123, Issue 22
Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and Staurosporine
journal, October 2000
- Walker, Edward H.; Pacold, Michael E.; Perisic, Olga
- Molecular Cell, Vol. 6, Issue 4
CLAMP©: a biosensor kinetic data analysis program
journal, April 1998
- Myszka, David G.; Morton, Thomas A.
- Trends in Biochemical Sciences, Vol. 23, Issue 4
Phosphoinositide 3-kinase inhibitor suppresses interleukin-17 expression in a murine asthma model
journal, March 2010
- Park, S. J.; Lee, K. S.; Kim, S. R.
- European Respiratory Journal, Vol. 36, Issue 6
Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma
journal, May 2014
- Flinn, Ian W.; Kahl, Brad S.; Leonard, John P.
- Blood, Vol. 123, Issue 22
The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia
journal, September 2011
- Hoellenriegel, Julia; Meadows, Sarah A.; Sivina, Mariela
- Blood, Vol. 118, Issue 13
A small molecule–kinase interaction map for clinical kinase inhibitors
journal, February 2005
- Fabian, Miles A.; Biggs, William H.; Treiber, Daniel K.
- Nature Biotechnology, Vol. 23, Issue 3
Discovery and in Vivo Evaluation of ( S )- N -(1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9 H -purin-6-amine (AMG319) and Related PI3Kδ Inhibitors for Inflammation and Autoimmune Disease
journal, July 2014
- Cushing, Timothy D.; Hao, Xiaolin; Shin, Youngsook
- Journal of Medicinal Chemistry, Vol. 58, Issue 1
Scaling and assessment of data quality
journal, December 2005
- Evans, Philip
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
The resurgence of covalent drugs
journal, April 2011
- Singh, Juswinder; Petter, Russell C.; Baillie, Thomas A.
- Nature Reviews Drug Discovery, Vol. 10, Issue 4
PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma
journal, February 2012
- Meadows, Sarah A.; Vega, Francisco; Kashishian, Adam
- Blood, Vol. 119, Issue 8
PI3 Kinase δ Is a Key Regulator of Synoviocyte Function in Rheumatoid Arthritis
journal, May 2012
- Bartok, Beatrix; Boyle, David L.; Liu, Yi
- The American Journal of Pathology, Vol. 180, Issue 5
Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction.
journal, April 1996
- Wymann, M. P.; Bulgarelli-Leva, G.; Zvelebil, M. J.
- Molecular and Cellular Biology, Vol. 16, Issue 4
Survival of leukemic B cells promoted by engagement of the antigen receptor
journal, November 2001
- Bernal, Alejandro; Pastore, Raymond D.; Asgary, Zahra
- Blood, Vol. 98, Issue 10
A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling
journal, May 2006
- Knight, Zachary A.; Gonzalez, Beatriz; Feldman, Morri E.
- Cell, Vol. 125, Issue 4
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis
journal, August 2004
- Firestein, Gary S.
- Journal of Clinical Investigation, Vol. 114, Issue 4
The p110δ structure: mechanisms for selectivity and potency of new PI(3)K inhibitors
journal, January 2010
- Berndt, Alex; Miller, Simon; Williams, Olusegun
- Nature Chemical Biology, Vol. 6, Issue 2
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Key role of the p110δ isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110δ function in B cells
journal, January 2006
- Bilancio, Antonio; Okkenhaug, Klaus; Camps, Montserrat
- Blood, Vol. 107, Issue 2
Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia
journal, March 2014
- Furman, Richard R.; Sharman, Jeff P.; Coutre, Steven E.
- New England Journal of Medicine, Vol. 370, Issue 11
Mechanisms and implications of phosphoinositide 3-kinase δ in promoting neutrophil trafficking into inflamed tissue
journal, May 2004
- Puri, Kamal D.; Doggett, Teresa A.; Douangpanya, Jason
- Blood, Vol. 103, Issue 9
A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL)
journal, May 2014
- Kahl, Brad S.; Spurgeon, Stephen E.; Furman, Richard R.
- Blood, Vol. 123, Issue 22
Role of PI3Kδ and PI3Kγ in inflammatory arthritis and tissue localization of neutrophils
journal, May 2008
- Randis, Tara M.; Puri, Kamal D.; Zhou, Hairu
- European Journal of Immunology, Vol. 38, Issue 5
Essential Role of Phosphoinositide 3-Kinase δ in Neutrophil Directional Movement
journal, March 2003
- Sadhu, Chanchal; Masinovsky, Boris; Dick, Ken
- The Journal of Immunology, Vol. 170, Issue 5
Essential role for the p110δ phosphoinositide 3-kinase in the allergic response
journal, October 2004
- Ali, Khaled; Bilancio, Antonio; Thomas, Matthew
- Nature, Vol. 431, Issue 7011
The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis
journal, August 2004
- Firestein, Gary S.
- Journal of Clinical Investigation, Vol. 114, Issue 4
Kinetic, equilibrium, and thermodynamic analysis of macromolecular interactions with BIACORE
book, January 2000
- Myszka, David G.
- Methods in Enzymology
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019
- Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman
- Nature Communications, Vol. 10, Issue 1
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021
- Tillu, Vikas A.; Rae, James; Gao, Ya
- Nature Communications, Vol. 12, Issue 1
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
Affinity analysis of non-steady-state data obtained under mass transport limited conditions using BIAcore technology
journal, September 1999
- Karlsson, Robert
- Journal of Molecular Recognition, Vol. 12, Issue 5
Role of PI3Kδ and PI3Kγ in inflammatory arthritis and tissue localization of neutrophils
journal, May 2008
- Randis, Tara M.; Puri, Kamal D.; Zhou, Hairu
- European Journal of Immunology, Vol. 38, Issue 5
PI3 Kinase δ Is a Key Regulator of Synoviocyte Function in Rheumatoid Arthritis
journal, May 2012
- Bartok, Beatrix; Boyle, David L.; Liu, Yi
- The American Journal of Pathology, Vol. 180, Issue 5
A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling
journal, May 2006
- Knight, Zachary A.; Gonzalez, Beatriz; Feldman, Morri E.
- Cell, Vol. 125, Issue 4
Extending the Range of Rate Constants Available from BIACORE: Interpreting Mass Transport-Influenced Binding Data
journal, August 1998
- Myszka, David G.; He, Xiaoyi; Dembo, Micah
- Biophysical Journal, Vol. 75, Issue 2
Discovery and in Vivo Evaluation of ( S )- N -(1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9 H -purin-6-amine (AMG319) and Related PI3Kδ Inhibitors for Inflammation and Autoimmune Disease
journal, July 2014
- Cushing, Timothy D.; Hao, Xiaolin; Shin, Youngsook
- Journal of Medicinal Chemistry, Vol. 58, Issue 1
Essential role for the p110δ phosphoinositide 3-kinase in the allergic response
journal, October 2004
- Ali, Khaled; Bilancio, Antonio; Thomas, Matthew
- Nature, Vol. 431, Issue 7011
BIRB-796 is not an effective ABL(T315I) inhibitor
journal, October 2005
- O'Hare, Thomas; Druker, Brian J.
- Nature Biotechnology, Vol. 23, Issue 10
The p110δ structure: mechanisms for selectivity and potency of new PI(3)K inhibitors
journal, January 2010
- Berndt, Alex; Miller, Simon; Williams, Olusegun
- Nature Chemical Biology, Vol. 6, Issue 2
The resurgence of covalent drugs
journal, April 2011
- Singh, Juswinder; Petter, Russell C.; Baillie, Thomas A.
- Nature Reviews Drug Discovery, Vol. 10, Issue 4
PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma
journal, March 2014
- Gopal, Ajay K.; Kahl, Brad S.; de Vos, Sven
- New England Journal of Medicine, Vol. 370, Issue 11
Rapid automated molecular replacement by evolutionary search
journal, February 1999
- Kissinger, Charles R.; Gehlhaar, Daniel K.; Fogel, David B.
- Acta Crystallographica Section D Biological Crystallography, Vol. 55, Issue 2
The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis
journal, October 2004
- Firestein, G. S.
- Journal of Clinical Investigation, Vol. 114, Issue 7
Key role of the p110δ isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110δ function in B cells
journal, January 2006
- Bilancio, Antonio; Okkenhaug, Klaus; Camps, Montserrat
- Blood, Vol. 107, Issue 2
PI3K p110δ regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
journal, March 2010
- Soond, Dalya R.; Bjørgo, Elisa; Moltu, Kristine
- Blood, Vol. 115, Issue 11
CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
journal, January 2011
- Lannutti, Brian J.; Meadows, Sarah A.; Herman, Sarah E. M.
- Blood, Vol. 117, Issue 2
The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia
journal, September 2011
- Hoellenriegel, Julia; Meadows, Sarah A.; Sivina, Mariela
- Blood, Vol. 118, Issue 13
PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma
journal, February 2012
- Meadows, Sarah A.; Vega, Francisco; Kashishian, Adam
- Blood, Vol. 119, Issue 8
Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma
journal, May 2014
- Flinn, Ian W.; Kahl, Brad S.; Leonard, John P.
- Blood, Vol. 123, Issue 22
Phosphoinositide 3-kinase inhibitor suppresses interleukin-17 expression in a murine asthma model
journal, March 2010
- Park, S. J.; Lee, K. S.; Kim, S. R.
- European Respiratory Journal, Vol. 36, Issue 6
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
Works referencing / citing this record:
PI3K isoform-selective inhibitors: next-generation targeted cancer therapies
journal, September 2015
- Wang, Xiang; Ding, Jian; Meng, Ling-hua
- Acta Pharmacologica Sinica, Vol. 36, Issue 10
Structural Determinants of Isoform Selectivity in PI3K Inhibitors
journal, February 2019
- Miller, Michelle; Thompson, Philip; Gabelli, Sandra
- Biomolecules, Vol. 9, Issue 3
Clinical Pharmacokinetic and Pharmacodynamic Profile of Idelalisib
journal, August 2015
- Ramanathan, Srinivasan; Jin, Feng; Sharma, Shringi
- Clinical Pharmacokinetics, Vol. 55, Issue 1
Theoretical studies on the selectivity mechanisms of PI3Kδ inhibition with marketed idelalisib and its derivatives by 3D-QSAR, molecular docking, and molecular dynamics simulation
journal, July 2019
- Zhu, Jingyu; Ke, Ke; Xu, Lei
- Journal of Molecular Modeling, Vol. 25, Issue 8
The PI3Kδ-Selective Inhibitor Idelalisib Minimally Interferes with Immune Effector Function Mediated by Rituximab or Obinutuzumab and Significantly Augments B Cell Depletion In Vivo
journal, February 2018
- Palazzo, Adam; Herter, Sylvia; Grosmaire, Laura
- The Journal of Immunology, Vol. 200, Issue 7
Discovery of the Potent Phosphoinositide 3‐Kinase δ (PI3 K δ) Inhibitors
journal, January 2020
- Lei, Tao; Hong, Yongwei; Chang, Xinyue
- ChemistrySelect, Vol. 5, Issue 1
Idelalisib for the treatment of non-Hodgkin lymphoma
journal, January 2016
- Graf, Solomon A.; Gopal, Ajay K.
- Expert Opinion on Pharmacotherapy, Vol. 17, Issue 2
Phosphoinositide 3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells
journal, August 2019
- Han, Haote; Chen, Na; Huang, Xionggao
- Journal of Biological Chemistry, Vol. 294, Issue 42
Discovery of a novel phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor against hematologic malignancies and theoretical studies on its PI3Kγ-specific binding mechanisms
journal, January 2019
- Zhu, Jingyu; Ke, Ke; Xu, Lei
- RSC Advances, Vol. 9, Issue 35
Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2- c ]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946)
journal, June 2016
- Scott, William J.; Hentemann, Martin F.; Rowley, R. Bruce
- ChemMedChem, Vol. 11, Issue 14
Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation
journal, January 2019
- Ma, Xiaodong; Fang, Fang; Tao, Qiangqiang
- MedChemComm, Vol. 10, Issue 3
Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1
journal, February 2017
- Dornan, Gillian L.; Siempelkamp, Braden D.; Jenkins, Meredith L.
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 8
Analysis of phosphoinositide 3-kinase inhibitors by bottom-up electron-transfer dissociation hydrogen/deuterium exchange mass spectrometry
journal, May 2017
- Masson, Glenn R.; Maslen, Sarah L.; Williams, Roger L.
- Biochemical Journal, Vol. 474, Issue 11
PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors
journal, February 2017
- Yahiaoui, Anella; Meadows, Sarah A.; Sorensen, Rick A.
- PLOS ONE, Vol. 12, Issue 2
Global kinome silencing combined with 3D invasion screening of the tumor microenvironment identifies fibroblast-expressed PIK3Cδ involvement in triple-negative breast cancer progression
posted_content, November 2019
- Gagliano, Teresa; Shah, Kalpit; Gargani, Sofia
- BioRxiv
Molecular dynamics insights for PI3K-δ inhibition & structure guided identification of novel PI3K-δ inhibitors
journal, November 2018
- Srivastava, Shubham; Singh Choudhary, Bhanwar; Mehta, Pakhuri
- Journal of Biomolecular Structure and Dynamics, Vol. 37, Issue 9
Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases
journal, May 2019
- Rodrigues, Daniel A.; Sagrillo, Fernanda S.; Fraga, Carlos A. M.
- Pharmaceuticals, Vol. 12, Issue 2
Molecular dynamics insights for PI3K-δ inhibition & structure guided identification of novel PI3K-δ inhibitors
text, January 2019
- Srivastava, Shubham; Choudhary, Bhanwar Singh; Mehta, Pakhuri
- Taylor & Francis
Molecular dynamics insights for PI3K-δ inhibition & structure guided identification of novel PI3K-δ inhibitors
text, January 2019
- Srivastava, Shubham; Choudhary, Bhanwar Singh; Mehta, Pakhuri
- Taylor & Francis
Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2- c ]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946)
journal, June 2016
- Scott, William J.; Hentemann, Martin F.; Rowley, R. Bruce
- ChemMedChem, Vol. 11, Issue 14
Analysis of phosphoinositide 3-kinase inhibitors by bottom-up electron-transfer dissociation hydrogen/deuterium exchange mass spectrometry
journal, May 2017
- Masson, Glenn R.; Maslen, Sarah L.; Williams, Roger L.
- Biochemical Journal, Vol. 474, Issue 11
Puquitinib, a novel orally available PI3Kδ inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia
journal, May 2017
- Xie, Chengying; He, Ye; Zhen, Mingyue
- Cancer Science, Vol. 108, Issue 7
PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors
journal, February 2017
- Yahiaoui, Anella; Meadows, Sarah A.; Sorensen, Rick A.
- PLOS ONE, Vol. 12, Issue 2
Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib
journal, August 2018
- Krause, Günter; Hassenrück, Floyd; Hallek, Michael
- Drug Design, Development and Therapy, Vol. Volume 12
Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential
journal, May 2016
- Barrientos, Jacqueline C.
- OncoTargets and Therapy
Structural Determinants of Isoform Selectivity in PI3K Inhibitors
journal, February 2019
- Miller, Michelle; Thompson, Philip; Gabelli, Sandra
- Biomolecules, Vol. 9, Issue 3
Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases
journal, May 2019
- Rodrigues, Daniel A.; Sagrillo, Fernanda S.; Fraga, Carlos A. M.
- Pharmaceuticals, Vol. 12, Issue 2
The PI3Kδ-Selective Inhibitor Idelalisib Minimally Interferes with Immune Effector Function Mediated by Rituximab or Obinutuzumab and Significantly Augments B Cell Depletion In Vivo
journal, February 2018
- Palazzo, Adam; Herter, Sylvia; Grosmaire, Laura
- The Journal of Immunology, Vol. 200, Issue 7