Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement

被引：177

作者：

Vasta, James D. ^{[1
]}

Corona, Cesear R. ^{[2
]}

Wilkinson, Jennifer ^{[1
]}

Zimprich, Chad A. ^{[1
]}

Hartnett, James R. ^{[1
]}

Ingold, Morgan R. ^{[1
]}

Zimmerman, Kristopher ^{[1
]}

Machleidt, Thomas ^{[1
]}

Kirkland, Thomas A. ^{[2
]}

Huwiler, Kristin G. ^{[1
]}

Ohana, Rachel Friedman ^{[1
]}

Slater, Michael ^{[1
]}

Otto, Paul ^{[1
]}

Cong, Mei ^{[1
]}

Wells, Carrow I. ^{[3
]}

Berger, Benedict-Tilman ^{[4
,5
]}

Hanke, Thomas ^{[4
]}

Glas, Carina ^{[6
,7
]}

Ding, Ke ^{[8
,9
]}

Drewry, David H. ^{[3
]}

Huber, Kilian V. M. ^{[6
,7
]}

Willson, Timothy M. ^{[3
]}

Knapp, Stefan ^{[4
,5
]}

Mueller, Susanne ^{[5
]}

Meisenheimer, Poncho L. ^{[2
]}

Fan, Frank ^{[1
]}

Wood, Keith V. ^{[1
]}

Robers, Matthew B. ^{[1
]}

机构：

[1] Promega Corp, 2800 Woods Hollow Rd, Fitchburg, WI 53711 USA

[2] Promega Biosci Inc, 277 Granada Dr, San Luis Obispo, CA 93401 USA

[3] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Struct Genom Consortium, Chapel Hill, NC USA

[4] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Struct Genom Consortium, Max von Laue Str 9, D-60438 Frankfurt, Germany

[5] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, Struct Genom Consortium, Max von Laue Str 9, D-60438 Frankfurt, Germany

[6] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium, Oxford, England

[7] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Oxford, England

[8] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, 190 Kaiyuan Ave, Guangzhou 510530, Guangdong, Peoples R China

[9] Jinan Univ, Sch Pharm, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China

来源：

CELL CHEMICAL BIOLOGY | 2018年 / 25卷 / 02期

基金：

英国惠康基金; 巴西圣保罗研究基金会; 加拿大创新基金会;

关键词：

TYROSINE KINASE; LIVING CELLS; BCR-ABL; INHIBITORS; BINDING; AFFINITY; ASSAY; IDENTIFICATION; LOCALIZATION; VALIDATION;

D O I：

10.1016/j.chembiol.2017.10.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

For kinase inhibitors, intracellular target selectivity is fundamental to pharmacological mechanism. Although a number of acellular techniques have been developed to measure kinase binding or enzymatic inhibition, such approaches can fail to accurately predict engagement in cells. Here we report the application of an energy transfer technique that enabled the first broad-spectrum, equilibrium-based approach to quantitatively profile target occupancy and compound affinity in live cells. Using this method, we performed a selectivity profiling for clinically relevant kinase inhibitors against 178 full-length kinases, and a mechanistic interrogation of the potency offsets observed between cellular and biochemical analysis. For the multikinase inhibitor crizotinib, our approach accurately predicted cellular potency and revealed improved target selectivity compared with biochemical measurements. Due to cellular ATP, a number of putative crizotinib targets are unexpectedly disengaged in live cells at a clinically relevant drug dose.

引用

页码：206 / +

页数：20

共 46 条

[1] The promise and peril of chemical probes [J].

Arrowsmith, Cheryl H. ;

Audia, James E. ;

Austin, Christopher ;

Baell, Jonathan ;

Bennett, Jonathan ;

Blagg, Julian ;

Bountra, Chas ;

Brennan, Paul E. ;

Brown, Peter J. ;

Bunnage, Mark E. ;

Buser-Doepner, Carolyn ;

Campbell, Robert M. ;

Carter, Adrian J. ;

Cohen, Philip ;

Copeland, Robert A. ;

Cravatt, Ben ;

Dahlin, Jayme L. ;

Dhanak, Dashyant ;

Edwards, Aled M. ;

Frye, Stephen V. ;

Gray, Nathanael ;

Grimshaw, Charles E. ;

Hepworth, David ;

Howe, Trevor ;

Huber, Kilian V. M. ;

Jin, Jian ;

Knapp, Stefan ;

Kotz, Joanne D. ;

Kruger, Ryan G. ;

Lowe, Derek ;

Mader, Mary M. ;

Marsden, Brian ;

Mueller-Fahrnow, Anke ;

Mueller, Susanne ;

O'Hagan, Ronan C. ;

Overington, John P. ;

Owen, Dafydd R. ;

Rosenberg, Saul H. ;

Roth, Brian ;

Ross, Ruth ;

Schapira, Matthieu ;

Schreiber, Stuart L. ;

Shoichet, Brian ;

Sundstrom, Michael ;

Superti-Furga, Giulio ;

Taunton, Jack ;

Toledo-Sherman, Leticia ;

Walpole, Chris ;

Walters, Michael A. ;

Willson, Timothy M. .

NATURE CHEMICAL BIOLOGY, 2015, 11 (08) :536-541

[2] Affinity Profiling of the Cellular Kinome for the Nucleotide Cofactors ATP, ADP, and GTP [J].

Becher, Isabelle ;

Savitski, Mikhail M. ;

Savitski, Maria Faelth ;

Hopf, Carsten ;

Bantscheff, Marcus ;

Drewes, Gerard .

ACS CHEMICAL BIOLOGY, 2013, 8 (03) :599-607

[3]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[4] A Type-II Kinase Inhibitor Capable of Inhibiting the T315I "Gatekeeper" Mutant of Bcr-Abl [J].

Choi, Hwan Geun ;

Ren, Pingda ;

Adrian, Francisco ;

Sun, Fangxian ;

Lee, Hyun Soo ;

Wang, Xia ;

Ding, Qiang ;

Zhang, Guobao ;

Xie, Yongping ;

Zhang, Jianming ;

Liu, Yi ;

Tuntland, Tove ;

Warmuth, Markus ;

Manley, Paul W. ;

Mestan, Juergen ;

Gray, Nathanael S. ;

Sim, Taebo .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (15) :5439-5448

[5] Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal-Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK) [J].

Cui, J. Jean ;

Tran-Dube, Michelle ;

Shen, Hong ;

Nambu, Mitchell ;

Kung, Pei-Pei ;

Pairish, Mason ;

Jia, Lei ;

Meng, Jerry ;

Funk, Lee ;

Botrous, Iriny ;

McTigue, Michele ;

Grodsky, Neil ;

Ryan, Kevin ;

Padrique, Ellen ;

Alton, Gordon ;

Timofeevski, Sergei ;

Yamazaki, Shinji ;

Li, Quhua ;

Zou, Helen ;

Christensen, James ;

Mroczkowski, Barbara ;

Bender, Steve ;

Kania, Robert S. ;

Edwards, Martin P. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (18) :6342-6363

[6] Comprehensive analysis of kinase inhibitor selectivity [J].

Davis, Mindy I. ;

Hunt, Jeremy P. ;

Herrgard, Sanna ;

Ciceri, Pietro ;

Wodicka, Lisa M. ;

Pallares, Gabriel ;

Hocker, Michael ;

Treiber, Daniel K. ;

Zarrinkar, Patrick P. .

NATURE BIOTECHNOLOGY, 2011, 29 (11) :1046-U124

[7] Identification of RIP1 kinase as a specific cellular target of necrostatins [J].

Degterev, Alexei ;

Hitomi, Junichi ;

Germscheid, Megan ;

Ch'en, Irene L. ;

Korkina, Olga ;

Teng, Xin ;

Abbott, Derek ;

Cuny, Gregory D. ;

Yuan, Chengye ;

Wagner, Gerhard ;

Hedrick, Stephen M. ;

Gerber, Scott A. ;

Lugovskoy, Alexey ;

Yuan, Junying .

NATURE CHEMICAL BIOLOGY, 2008, 4 (05) :313-321

[8] Progress towards a public chemogenomic set for protein kinases and a call for contributions [J].

Drewry, David H. ;

Wells, Carrow I. ;

Andrews, David M. ;

Angell, Richard ;

Al-Ali, Hassan ;

Axtman, Alison D. ;

Capuzzi, Stephen J. ;

Elkins, Jonathan M. ;

Ettmayer, Peter ;

Frederiksen, Mathias ;

Gileadi, Opher ;

Gray, Nathanael ;

Hooper, Alice ;

Knapp, Stefan ;

Laufer, Stefan ;

Luecking, Ulrich ;

Michaelides, Michael ;

Mueller, Susanne ;

Muratov, Eugene ;

Denny, R. Aldrin ;

Saikatendu, Kumar S. ;

Treiber, Daniel K. ;

Zuercher, William J. ;

Willson, Timothy M. .

PLOS ONE, 2017, 12 (08)

[9] Comprehensive characterization of the Published Kinase Inhibitor Set [J].

Elkins, Jonathan M. ;

Fedele, Vita ;

Szklarz, Marta ;

Azeez, Kamal R. Abdul ;

Salah, Eidarus ;

Mikolajczyk, Jowita ;

Romanov, Sergei ;

Sepetov, Nikolai ;

Huang, Xi-Ping ;

Roth, Bryan L. ;

Zen, Ayman Al Haj ;

Fourches, Denis ;

Muratov, Eugene ;

Tropsha, Alex ;

Morris, Joel ;

Teicher, Beverly A. ;

Kunkel, Mark ;

Polley, Eric ;

Lackey, Karen E. ;

Atkinson, Francis L. ;

Overington, John P. ;

Bamborough, Paul ;

Mueller, Susanne ;

Price, Daniel J. ;

Willson, Timothy M. ;

Drewry, David H. ;

Knapp, Stefan ;

Zuercher, William J. .

NATURE BIOTECHNOLOGY, 2016, 34 (01) :95-103

[10] A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis [J].

Fauster, A. ;

Rebsamen, M. ;

Huber, K. V. M. ;

Bigenzahn, J. W. ;

Stukalov, A. ;

Lardeau, C-H ;

Scorzoni, S. ;

Bruckner, M. ;

Gridling, M. ;

Parapatics, K. ;

Colinge, J. ;

Bennett, K. L. ;

Kubicek, S. ;

Krautwald, S. ;

Linkermann, A. ;

Superti-Furga, G. .

CELL DEATH & DISEASE, 2015, 6 :e1767-e1767

← 1 2 3 4 5 →