Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase
dc.contributor.author | Johnson, Taylor K. | |
dc.contributor.author | Bochar, Daniel A. | |
dc.contributor.author | Vandecan, Nathalie M. | |
dc.contributor.author | Furtado, Jessica | |
dc.contributor.author | Agius, Michael P. | |
dc.contributor.author | Phadke, Sameer | |
dc.contributor.author | Soellner, Matthew B. | |
dc.date.accessioned | 2021-09-08T14:36:36Z | |
dc.date.available | 2022-10-08 10:36:35 | en |
dc.date.available | 2021-09-08T14:36:36Z | |
dc.date.issued | 2021-09-06 | |
dc.identifier.citation | Johnson, Taylor K.; Bochar, Daniel A.; Vandecan, Nathalie M.; Furtado, Jessica; Agius, Michael P.; Phadke, Sameer; Soellner, Matthew B. (2021). "Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase." Angewandte Chemie 133(37): 20358-20361. | |
dc.identifier.issn | 0044-8249 | |
dc.identifier.issn | 1521-3757 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/169317 | |
dc.description.abstract | Allosteric inhibitors of Abl kinase are being explored in the clinic, often in combination with ATP‐site inhibitors of Abl kinase. However, there are conflicting data on whether both ATP‐competitive inhibitors and myristoyl‐site allosteric inhibitors can simultaneously bind Abl kinase. Here, we determine whether there is synergy or antagonism between ATP‐competitive inhibitors and allosteric inhibitors of Abl. We observe that clinical ATP‐competitive inhibitors are not synergistic with allosteric ABL inhibitors, however, conformation‐selective ATP‐site inhibitors that modulate the global conformation of Abl can afford synergy. We demonstrate that kinase conformation is the key driver to simultaneously bind two compounds to Abl kinase. Finally, we explore the interaction of allosteric and conformation selective ATP‐competitive inhibitors in a series of biochemical and cellular assays.We describe a better understanding of the interaction between allosteric and ATP‐competitive inhibitors of Abl. Using a protease accessibility assay we developed, we determined the global conformation of Abl when bound to Abl inhibitors. We found that synergy between ATP‐competitive and allosteric inhibitors of Abl required a „matched“ kinase conformation. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.subject.other | Abl | |
dc.subject.other | allostery | |
dc.subject.other | inhibitors | |
dc.subject.other | kinase | |
dc.subject.other | synergy | |
dc.title | Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Materials Science and Engineering | |
dc.subject.hlbsecondlevel | Chemistry | |
dc.subject.hlbsecondlevel | Chemical Engineering | |
dc.subject.hlbtoplevel | Engineering | |
dc.subject.hlbtoplevel | Science | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/169317/1/ange202105351_am.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/169317/2/ange202105351.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/169317/3/ange202105351-sup-0001-misc_information.pdf | |
dc.identifier.doi | 10.1002/ange.202105351 | |
dc.identifier.source | Angewandte Chemie | |
dc.identifier.citedreference | T. O’Hare, C. A. Eide, M. W. Deininger, Clin. Lymphoma Myeloma Leuk. 2017, 7, S120 – S130. | |
dc.identifier.citedreference | J. E. Cortes, D. W. Kim, J. Pinilla-Ibarz, P. le Coutre, R. Paquette, C. Chuah, F. E. Nicolini, J. F. Apperley, H. J. Khoury, M. Talpaz, J. DiPersio, J. D. DeAngelo, E. Abruzzese, D. Rea, M. Baccarani, M. C. Müller, C. Gambacorti-Passerini, S. Wong, S. Lustgarten, V. M. Rivera, T. Clackson, C. D. Turner, F. G. Haluska, F. Guilhot, M. W. Deininger, A. Hochhaus, T. Hughes, J. M. Goldman, N. P. Shah, H. Kantarjian, N. Engl. J. Med. 2013, 369, 1783 – 1796. | |
dc.identifier.citedreference | F. J. Adrián, Q. Ding, T. Sim, A. Velentza, C. Sloan, Y. Liu, G. Zhang, W. Hur, S. Ding, P. Manley, J. Mestan, D. Fabbro, N. S. Gray, Nat. Chem. Biol. 2006, 2, 95 – 102. | |
dc.identifier.citedreference | R. E. Iacob, J. Zhang, N. S. Gray, J. R. Engen, PLoS One 2011, 6, e15929. | |
dc.identifier.citedreference | J. Zhang, F. J. Adrián, W. Jahnke, S. W. Cowan-Jacob, A. G. Li, R. E. Iacob, T. Sim, J. Powers, C. Dierks, F. Sun, G. R. Guo, Q. Ding, B. Okram, Y. Choi, A. Wojciechowski, X. Deng, G. Liu, G. Fendrich, A. Strauss, N. Vajpai, S. Grzesiek, T. Tuntland, Y. Liu, B. Bursulaya, M. Azam, P. W. Manley, J. R. Engen, G. Q. Daley, M. Warmuth, N. S. Gray, Nature 2010, 463, 501 – 506. | |
dc.identifier.citedreference | B. Nagar, O. Hantschel, M. A. Young, K. Scheffzek, D. Veach, W. Bornmann, B. Clarkson, G. Superti-Furga, J. Kuriyan, Cell 2003, 112, 859 – 871. | |
dc.identifier.citedreference | T.-C. Chou, Cancer Res. 2010, 70, 440 – 446. | |
dc.identifier.citedreference | M. P. Agius, K. S. Ko, T. K. Johnson, F. E. Kwarcinski, S. Phadke, E. J. Lachacz, M. B. Soellner, ACS Chem. Biol. 2019, 14, 1556 – 1563. | |
dc.identifier.citedreference | T.-C. Chou, Pharmacol. Rev. 2007, 58, 621 – 681. | |
dc.identifier.citedreference | L. Skora, J. Mestan, D. Fabbro, W. Jahnke, S. Grzesiek, Proc. Natl. Acad. Sci. USA 2013, 110, E4437 - E4445. | |
dc.identifier.citedreference | D. Fabbro, P. W. Manley, W. Jahnke, J. Liebetanz, A. Szyttenholm, G. Fendrich, A. Strauss, J. Zhang, N. S. Gray, F. Adrian, M. Warmuth, X. Pelle, R. Grotzfeld, F. Berst, A. Marzinzik, S. W. Cowan-Jacob, P. Furet, J. Mestan, Biochim. Biophys. Acta Proteins Proteomics 2010, 1804, 454 – 462. | |
dc.identifier.citedreference | M. Khateb, N. Ruimi, H. Khamisie, Y. Najajreh, A. Mian, A. Metodieva, M. Ruthardt, J. Mahajna, BMC Cancer 2012, 12, 563 – 572. | |
dc.identifier.citedreference | R. Kurzrock, J. U. Gutterman, M. Talpaz, N. Engl. J. Med. 1988, 319, 990 – 998. | |
dc.identifier.citedreference | B. J. Druker, F. Guilhot, S. G. O’Brien, I. Gathmann, H. Kantarjian, N. Gattermann, M. W. N. Deininger, R. T. Silver, J. M. Goldman, R. M. Stone, F. Cervantes, A. Hochhaus, B. L. Powell, J. L. Gabrilove, P. Rousselot, J. Reiffers, J. J. Cornelissen, T. Hughes, H. Agis, T. Fischer, G. Verhoef, J. Shepherd, G. Saglio, A. Gratwohl, J. L. Nielsen, J. P. Radich, B. Simonsson, K. Taylor, M. Baccarani, L. Letvak, R. A. Larson, N. Engl. J. Med. 2006, 355, 2408 – 2417. | |
dc.identifier.citedreference | V. Prasad, S. Mailankody, JAMA J. Am. Med. Assoc. 2014, 311, 353 – 354. | |
dc.identifier.citedreference | F. E. Kwarcinski, K. R. Brandvold, S. Phadke, O. M. Beleh, T. K. Johnson, J. L. Meagher, M. A. Seeliger, J. A. Stuckey, M. B. Soellner, ACS Chem. Biol. 2016, 11, 1296 – 1304. | |
dc.identifier.citedreference | O. Hantschel, B. Nagar, S. Guettler, J. Kretzschmar, K. Dorey, J. Kuriyan, G. Superti-Furga, Cell 2003, 112, 845 – 857. | |
dc.identifier.citedreference | S. Panjarianm, R. E. Iacob, S. Chen, T. E. Wales, J. R. Engen, T. E. Smithgall, J. Biol. Chem. 2013, 288, 6116 – 6129. | |
dc.identifier.citedreference | F. Grebien, O. Hantschel, J. Wojcik, I. Kaupe, B. Kovacic, A. M. Wyrzucki, G. D. Gish, S. Cerny-Reiterer, A. Koide, H. Beug, T. Pawson, P. Valent, S. Koide, G. Superti-Furga, Cell 2011, 147, 306 – 319. | |
dc.identifier.citedreference | P. Filippakopoulos, M. Kofler, O. Hantschel, G. D. Gish, F. Grebien, E. Salah, P. Neudecker, L. E. Kay, B. E. Turk, G. Superti-Furga, T. Pawson, S. Knapp, Cell 2016, 134, 793 – 803. | |
dc.identifier.citedreference | T.-C. Chou, P. Talalay, Adv. Enzyme Regul. 1984, 22, 27 – 55. | |
dc.working.doi | NO | en |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.