Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis
Open accessAbstract
Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor-dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btk inhibition abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. Accordingly, in myeloid- and FcγR-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell- or myeloid cell-driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.
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The parent inhibitor CGI1746 does not inhibit HCK.
“The parent inhibitor CGI1746 used for our degraders does not inhibit HCK, 29”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [29]
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Fcγ receptors as regulators of immune responses
Nimmerjahn, F., & Ravetch, J. V. (2008) · Nature Reviews Immunology · doi:10.1038/nri2206 · Cited by 2,947 · see citing works
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466 · see citing works
A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib)
Wood, E. R., Truesdale, A. T., McDonald, O. B., Yuan, D. Y., Hassell, A. M., Dickerson, S. H., Ellis, B., Pennisi, C., Horne, E., Lackey, K. E., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1168 · Cited by 1,125 · see citing works
Rational design of inhibitors that bind to inactive kinase conformations
Liu, Y., & Gray, N. S. (2006) · Nature Chemical Biology · doi:10.1038/nchembio799 · Cited by 1,096 · see citing works
Roles of Fc receptors in autoimmunity
Takai, T. (2002) · Nature reviews. Immunology · doi:10.1038/nri856 · Cited by 627 · see citing works
Crystal Structure of Hck in Complex with a Src Family–Selective Tyrosine Kinase Inhibitor
Schindler, T. H., Sicheri, F., Pico, A. R., Gazit, A., Levitzki, A., & Kuriyan, J. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80357-3 · Cited by 429 · see citing works
Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis
Nell, V. P. K., Machold, K. P., Stamm, T. A., Eberl, G., Heinzl, H., Uffmann, M., Smolen, J. S., & Steiner, G. E. (2005) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2005.035691 · Cited by 354 · see citing works
B‐lymphocyte contributions to human autoimmune disease
Yanaba, K., Bouaziz, J., Matsushita, T., MAGRO, C. M. J., Clair, E. W. S., & Tedder, T. F. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00646.x · Cited by 327 · see citing works
Tyrosine Kinases Btk and Tec Regulate Osteoclast Differentiation by Linking RANK and ITAM Signals
Shinohara, M., Koga, T., Okamoto, K., Sakaguchi, S., Arai, K., Yasuda, H., Takai, T., Kodama, T., Morio, T., Geha, R. S., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.037 · Cited by 321 · see citing works
Therapeutic B cell depletion impairs adaptive and autoreactive CD4 + T cell activation in mice
Bouaziz, J., Yanaba, K., Venturi, G. M., Wang, Y., Tisch, R., Poe, J. C., & Tedder, T. F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709205105 · Cited by 315 · see citing works
Clavel, C., Nogueira, L., Laurent, L., Iobagiu, C., Vincent, C., Sebbag, M., & Serre, G. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23284 · Cited by 278 · see citing works
Chemical Genetics: Where Genetics and Pharmacology Meet
Knight, Z. A., & Shokat, K. M. (2007) · Cell · doi:10.1016/j.cell.2007.01.021 · Cited by 244 · see citing works
The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases
Hamilton, J. A., & Tak, P. P. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24505 · Cited by 217 · see citing works
Kagari, T., Doi, H., & Shimozato, T. (2002) · Journal of Immunology · doi:10.4049/jimmunol.169.3.1459 · Cited by 212 · see citing works
The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective
Satterthwaite, A. B., & Witte, O. N. (2000) · Immunological Reviews · doi:10.1111/j.1600-065x.2000.imr017504.x · Cited by 209 · see citing works
Bruton’s Tyrosine Kinase Is Required for TLR2 and TLR4-Induced TNF, but Not IL-6, Production
Horwood, N. J., Page, T. H., McDaid, J., Palmer, C. D., Campbell, J., Mahon, T., Brennan, F. M., Webster, D., & Foxwell, B. M. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.6.3635 · Cited by 203 · see citing works
Lindvall, J. M., Blomberg, K. E. M., Väliaho, J., Vargas, L., Heinonen, J. E., Berglöf, A., Mohamed, A. J., Nore, B. F., Vihinen, M., & Smith, C. I. E. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00225.x · Cited by 199 · see citing works
The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective
Satterthwaite, A. B., & Witte, O. N. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.017504.x · Cited by 197 · see citing works
Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig.
Knoerzer, D. B., Karr, R. W., Schwartz, B. D., & Mengle-Gaw, L. J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118146 · Cited by 161 · see citing works
Marcotte, D. J., Liu, Y., Arduini, R. M., Hession, C. A., Miatkowski, K., Wildes, C. P., Cullen, P. F., Hong, V. S., Hopkins, B. T., Mertsching, E., et al. (2010) · Protein Science · doi:10.1002/pro.321 · Cited by 158 · see citing works
Regulation of B Lymphocyte Development and Activation by Bruton's Tyrosine Kinase
Khan, W. N. (2001) · Immunologic Research · doi:10.1385/ir:23:2-3:147 · Cited by 156 · see citing works
Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression
Cook, A. D., Rowley, M. J., Mackay, I. R., Gough, A., & Emery, P. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780391015 · Cited by 149 · see citing works
Yanaba, K., Hamaguchi, Y., Venturi, G. M., Steeber, D. A., Clair, E. W. S., & Tedder, T. F. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.1369 · Cited by 145 · see citing works
(2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.00611.x · Cited by 138 · see citing works
Watanabe, D., Hashimoto, S., Ishiai, M., Matsushita, M., Baba, Y., Kishimoto, T., Kurosaki, T., & Tsukada, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103675200 · Cited by 136 · see citing works
A crucial role for macrophages in the pathology of K/B × N serum‐induced arthritis
Solomon, S., Rajasekaran, N., Jeisy‐Walder, E., Snapper, S. B., & Illges, H. (2005) · European Journal of Immunology · doi:10.1002/eji.200526167 · Cited by 135 · see citing works
Jongstra‐Bilen, J., Cano, A. P., Hasija, M., Xiao, H., Smith, C. I. E., & Cybulsky, M. I. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.288 · Cited by 132 · see citing works
Mangla, A. G., Khare, A., Varanasi, V., Panday, N. N., Mukhopadhyay, A., Ravindran, B., Bal, V., George, A., & Rath, S. (2004) · Blood · doi:10.1182/blood-2004-01-0207 · Cited by 128 · see citing works
Sharma, S., Orlowski, G. M., & Song, W. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.329 · Cited by 126 · see citing works
Mechanism of B-Cell Receptor-Induced Phosphorylation and Activation of Phospholipase C-γ2
Kim, Y. J., Sekiya, F., Poulin, B., Bae, Y. S., & Rhee, S. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.9986-9999.2004 · Cited by 126 · see citing works
The role of antibodies in mouse models of rheumatoid arthritis, and relevance to human disease.
Monach, P., Benoist, C., & Mathis, D. (2004) · Advances in Immunology · doi:10.1016/s0065-2776(04)82005-4 · Cited by 118 · see citing works
Essential Role of Fcγ Receptors in Anti-Type II Collagen Antibody-Induced Arthritis
Kagari, T., Tanaka, D., Doi, H., & Shimozato, T. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.4318 · Cited by 114 · see citing works
Role of Bruton's tyrosine kinase in immunodeficiency
Tsukada, S., Rawlings, D. J., & Witte, O. N. (1994) · Current Opinion in Immunology · doi:10.1016/0952-7915(94)90151-1 · Cited by 112 · see citing works
The Tec Family Tyrosine Kinase Btk Regulates RANKL-induced Osteoclast Maturation
Lee, S. H., Kim, T. S., Jeong, D., Kim, N., & Choi, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708935200 · Cited by 106 · see citing works
Humphries, L. A., Dangelmaier, C., Sommer, K., Kipp, K. R., Kato, R. M., Griffith, N., Bakman, I., Turk, C. W., Daniel, J. L., & Rawlings, D. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311985200 · Cited by 103 · see citing works
Bruton's Tyrosine Kinase is involved in innate and adaptive immunity.
Brunner, C., Müller, B., & Wirth, T. C. (2005) · PubMed · doi:10.14670/hh-20.945 · Cited by 102 · see citing works
Katschke, K. J., Helmy, K. Y., Steffek, M., Xi, H., Yin, J., Lee, W. P., Gribling, P., Barck, K. H., Carano, R. A. D., Taylor, R. E., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070432 · Cited by 100 · see citing works
Self-citationThe Role of Tec Family Kinases in Myeloid Cells
Schmidt, U., Boucheron, N., Unger, B., & Ellmeier, W. (2004) · International Archives of Allergy and Immunology · doi:10.1159/000078339 · Cited by 92 · see citing works
Genes on the X chromosome affect development of collagen-induced arthritis in mice
Jansson, L., & Holmdahl, R. (1993) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1993.tb08218.x · Cited by 85 · see citing works
Autoantibodies to citrullinated proteins: ACPA
Vincent, C., Nogueira, L., Clavel, C., Sebbag, M., & Serre, G. (2005) · Autoimmunity · doi:10.1080/08916930400022582 · Cited by 75 · see citing works
Palmer, C. D., Mutch, B. E., Workman, S., McDaid, J., Horwood, N. J., & Foxwell, B. M. J. (2007) · Blood · doi:10.1182/blood-2007-07-102343 · Cited by 73 · see citing works
Mullazehi, M., Mathsson, L., Lampa, J., & Rönnelid, J. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21892 · Cited by 73 · see citing works
Thabet, M. M., Huizinga, T. W. J., Marques, R. B., Stoeken‐Rijsbergen, G., Bakker, A. M., Kurreeman, F. A. S., White, S. J., Toes, R. E. M., & Mil, A. H. M. V. D. H. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.099309 · Cited by 53 · see citing works
ANTIBODIES TO TYPE II COLLAGEN IN EARLY RHEUMATOID ARTHRITIS
Morgan, K., Clague, R. B., REYNOLDS, I., & Davis, M. R. (1993) · Lara D. Veeken · doi:10.1093/rheumatology/32.4.333 · Cited by 47 · see citing works
Goldstein, M. D., Debenedette, M. A., Hollenbaugh, D. L., & Watts, T. H. (1996) · Molecular Immunology · doi:10.1016/0161-5890(96)00005-3 · Cited by 33 · see citing works
Bruton's tyrosine kinase as a drug discovery target
Pan, Z. (2008) · Drug News & Perspectives · doi:10.1358/dnp.2008.21.7.1255308 · Cited by 30 · see citing works
Activation Loop Phosphorylation Modulates Bruton’s Tyrosine Kinase (Btk) Kinase Domain Activity
Lin, L., Czerwiński, R., Kelleher, K. S., Siegel, M. M., Wu, P. W., Kriz, R., AULABAUGH, A. E., & Stahl, M. (2009) · Biochemistry · doi:10.1021/bi8019756 · Cited by 24 · see citing works
The complex role of Fcγ receptors in the pathology of arthritis
Boross, P., & Verbeek, J. S. (2006) · Springer Seminars in Immunopathology · doi:10.1007/s00281-006-0049-9 · Cited by 23 · see citing works
B cell-directed therapy in rheumatoid arthritis--clinical experience.
Panayi, G. S. (2005) · PubMed · Cited by 18 · see citing works
FcγRIII‐Expressing Macrophages are Essential for Development of Collagen‐Induced Arthritis
Andr�en, M., Xiang, Z., Nilsson, G. P., & Kleinau, S. (2006) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2006.01743.x · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Currie, K.S., DeSimone, R.W., Mitchell, S.A. & Pippin, D.A. Certain heterocyclic substituted imidazo[1,2-a]pyrazin-8-yl compounds and methods of inhibition of Bruton's tyrosine kinase by such compounds. US Patent 7,393,848 (2008).
Cited by
Sorted by citations
Borst, O., Walker, B., Münzer, P., Russo, A., Schmid, E., Faggio, C., Bigalke, B., Laufer, S., Gawaz, M., & Lang, F. J. W. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350110 · Cited by 1,867 · see citing works
Pathogenetic insights from the treatment of rheumatoid arthritis
McInnes, I. B., & Schett, G. A. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31472-1 · Cited by 1,353 · see citing works
PROTACs: past, present and future
Li, K., & Crews, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00193d · Cited by 869 · see citing works
B cell depletion therapies in autoimmune disease: advances and mechanistic insights
Lee, D. S. W., Rojas, O. L., & Gommerman, J. L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00092-2 · Cited by 666 · see citing works
Targeting Bruton's tyrosine kinase in B cell malignancies
Hendriks, R. W., Yuvaraj, S., & Kil, L. P. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3702 · Cited by 564 · see citing works
Prolonged and tunable residence time using reversible covalent kinase inhibitors
Bradshaw, J. M., McFarland, J. M., Paavilainen, V. O., Bisconte, A. R., Tam, D., Phan, V. T., Romanov, S., Finkle, D., Shu, J., Patel, V. P., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1817 · Cited by 428 · see citing works
Kinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431 · see citing works
Guo, Y., Liu, Y., Hu, N., Yu, D., Zhou, C., Shi, G., Zhang, B., Wei, M., Liu, J., Luo, L., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00687 · Cited by 372 · see citing works
Chemistries of bifunctional PROTAC degraders
Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313 · see citing works
Drug–Target Kinetics in Drug Discovery
Tonge, P. J. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00185 · Cited by 295 · see citing works
The ins and outs of selective kinase inhibitor development
Müller, S., Chaikuad, A., Gray, N. S., & Knapp, S. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1938 · Cited by 276 · see citing works
Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity
Weber, A. N. R., Bittner, Z., Liu, X., Dang, T., Radsak, M. P., & Brunner, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01454 · Cited by 271 · see citing works
Walter, H. S., Rule, S. A., Dyer, M. J. S., Karlin, L., Jones, C. H., Cazin, B., Quittet, P., Shah, N., Hutchinson, C. V., Honda, H., et al. (2015) · Blood · doi:10.1182/blood-2015-08-664086 · Cited by 270 · see citing works
Crawford, J. J., Johnson, A. R., Misner, D., Belmont, L. D., Castanedo, G. M., Choy, R., Coraggio, M., Dong, L., Eigenbrot, C. W., Erickson, R., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01712 · Cited by 263 · see citing works
Self-citationIbrutinib and novel BTK inhibitors in clinical development
Akinleye, A., Chen, Y., Mukhi, N., Song, Y., & Liu, D. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-59 · Cited by 233 · see citing works
Evans, E. K., Tester, R. W., Aslanian, S., Karp, R., Sheets, M. P., Labenski, M., Witowski, S. R., Lounsbury, H. A., Chaturvedi, P., Mazdiyasni, H., et al. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.203489 · Cited by 223 · see citing works
Ibrutinib antagonizes rituximab-dependent NK cell–mediated cytotoxicity
Kohrt, H. E. K., Sagiv-Barfi, I., Rafiq, S., Herman, S. E. M., Butchar, J. P., Cheney, C. M., Zhang, X., Buggy, J. J., Muthusamy, N., Levy, R., et al. (2014) · Blood · doi:10.1182/blood-2014-01-547869 · Cited by 218 · see citing works
Bruton tyrosine kinase inhibitors for multiple sclerosis
Krämer, J., Bar-Or, A., Turner, T. J., & Wiendl, H. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00800-7 · Cited by 206 · see citing works
Bender, A. T., Gardberg, A. S., Pereira, A., Johnson, T. L., Wu, Y., Grenningloh, R., Head, J. C., Morandi, F., Haselmayer, P., & Liu‐Bujalski, L. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.107037 · Cited by 199 · see citing works
Angst, D., Gessier, F., Janser, P., Vulpetti, A., Wälchli, R., Beerli, C., Littlewood-Evans, A. J., Dawson, J., Nuesslein‐Hildesheim, B., Wieczorek, G., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01916 · Cited by 179 · see citing works
The development of Bruton's tyrosine kinase (BTK) inhibitors from 2012 to 2017: A mini-review
Liang, C., Tian, D., Ren, X., Ding, S., Jia, M., Xin, M., & Thareja, S. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.03.062 · Cited by 178 · see citing works
Bruton tyrosine kinase degradation as a therapeutic strategy for cancer
Dobrovolsky, D., Wang, E. S., Morrow, S., Leahy, C., Faust, T., Nowak, R. P., Donovan, K. A., Yang, G., Li, Z., Fischer, E. S., et al. (2019) · Blood · doi:10.1182/blood-2018-07-862953 · Cited by 169 · see citing works
Tai, Y., Chang, B. Y., Kong, S., Fulciniti, M., Yang, G., Calle, Y., Hu, Y., Lin, J., Zhao, J., Cagnetta, A., et al. (2012) · Blood · doi:10.1182/blood-2011-12-396853 · Cited by 165 · see citing works
Alu, A., Lei, H., Han, X., Wei, Y., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01353-w · Cited by 157 · see citing works
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765)
Burger, J. A., & Buggy, J. J. (2013) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2013.777837 · Cited by 156 · see citing works
Watterson, S. H., Lucca, G. V. D., Shi, Q., Langevine, C. M., Liu, Q., Batt, D. G., Bertrand, M. B., Gong, H., Dai, J., Yip, S. H., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01088 · Cited by 153 · see citing works
Caldwell, R. D., Qiu, H., Askew, B. C., Bender, A. T., Brügger, N., Camps, M., Dhanabal, M., Dutt, V., Eichhorn, T., Gardberg, A. S., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00794 · Cited by 150 · see citing works
Self-citationEfficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models
Haselmayer, P., Camps, M., Liu‐Bujalski, L., Nguyen, N. T. K., Morandi, F., Head, J. C., O’Mahony, A., Zimmerli, S. C., Bruns, L., Bender, A. T., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1800583 · Cited by 143 · see citing works
The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy
Crofford, L. J., Nyhoff, L. E., Sheehan, J. H., & Kendall, P. L. (2016) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2016.1152888 · Cited by 142 · see citing works
Xu, D., Kim, Y. D., Postelnek, J., Vu, M. D., Hu, D., Liao, C., Bradshaw, M., Hsu, J., Zhang, J., Pashine, A., et al. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.187740 · Cited by 142 · see citing works
Self-citationA public-private partnership to unlock the untargeted kinome
Knapp, S., Arruda, P., Blagg, J., Burley, S. K., Drewry, D. H., Edwards, A. M., Fabbro, D., Gillespie, P., Gray, N. S., Küster, B., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1113 · Cited by 139 · see citing works
BTK Signaling in B Cell Differentiation and Autoimmunity
Corneth, O. B. J., Wolterink, R. G. J. K., & Hendriks, R. W. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_478 · Cited by 140 · see citing works
Battling Btk mutants with noncovalent inhibitors that overcome Cys481 and Thr474 mutations
Johnson, A. R., Kohli, P. B., Katewa, A., Gogol, E., Belmont, L. D., Choy, R., Penuel, E., Burton, L., Eigenbrot, C., Yu, C., et al. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00480 · Cited by 137 · see citing works
Self-citationLiu, X., Pichulik, T., Wolz, O., Dang, T., Stutz, A., Dillen, C. A., Garcia, M. D., Kraus, H., Dickhöfer, S., Daiber, E., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.01.017 · Cited by 132 · see citing works
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
Bogdos, M. K., Pinard, E., & Murphy, J. A. (2018) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.14.179 · Cited by 129 · see citing works
Ponader, S., & Burger, J. A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.1046 · Cited by 123 · see citing works
Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate
Wang, Q., Vogan, E. M., Nocka, L. M., Rosen, C. E., Zorn, J. A., Harrison, S. C., & Kuriyan, J. (2015) · eLife · doi:10.7554/elife.06074 · Cited by 125 · see citing works
Watterson, S. H., Liu, Q., Bertrand, M. B., Batt, D. G., Li, L., Pattoli, M. A., Skala, S., Cheng, L., Obermeier, M. T., Moore, R., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00167 · Cited by 120 · see citing works
Phenazinium Salt-Catalyzed Aerobic Oxidative Amidation of Aromatic Aldehydes
Leow, D. (2014) · Organic Letters · doi:10.1021/ol5029354 · Cited by 119 · see citing works
CGI1746 targets σ1R to modulate ferroptosis through mitochondria-associated membranes
Zhang, Z., Zhou, H., Gu, W., Wei, Y., Mou, S., Wang, Y., Zhang, J., & Zhong, Q. (2024) · Nature Chemical Biology · doi:10.1038/s41589-023-01512-1 · Cited by 124 · see citing works
Self-citationSelective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis
Rankin, A. L., Seth, N., Keegan, S., Andreyeva, T., Cook, T. A., Edmonds, J., Mathialagan, N., Benson, M. J., Syed, J., Zhan, Y., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301553 · Cited by 113 · see citing works
Lou, Y. C., Han, X., Kuglstatter, A., Kondru, R. K., Sweeney, Z. K., Soth, M., McIntosh, J. E., Litman, R., Suh, J. M., Koçer, B., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500305p · Cited by 112 · see citing works
Smith, P. F., Krishnarajah, J., Nunn, P. A., Hill, R. J., Karr, D. E., Tam, D., Masjedizadeh, M. R., Funk, J. O., & Gourlay, S. G. (2017) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13351 · Cited by 108 · see citing works
Corneth, O. B. J., Verstappen, G. M. P. J., Paulissen, S. M. J., de Bruijn, M. J. W., Rip, J., Lukkes, M. M., van Hamburg, J. P., Lubberts, E., Bootsma, H., Kroese, F. G. M., et al. (2017) · Arthritis & Rheumatology · doi:10.1002/art.40059 · Cited by 108 · see citing works
Murthy, P., Durco, F., Miller-Ocuin, J. L., Takedai, T., Shankar, S., Liang, X., Liu, X., Cui, X. D., Sachdev, U., Rath, D., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.12.161 · Cited by 107 · see citing works
Qorraj, M., Bruns, H., Böttcher, M., Weigand, L., Saul, D., Mackensen, A., Jitschin, R., & Mougiakakos, D. (2016) · Leukemia · doi:10.1038/leu.2016.214 · Cited by 104 · see citing works
Bruton’s Tyrosine Kinase (BTK) Inhibitors in Clinical Trials
Burger, J. A. (2013) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-013-0188-8 · Cited by 100 · see citing works
Small-Molecule Kinase Inhibitors for the Treatment of Nononcologic Diseases
Xie, Z., Yang, X., Duan, Y., Han, J., & Liao, C. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01511 · Cited by 102 · see citing works
Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease
von Hundelshausen, P., & Siess, W. (2021) · Cancers · doi:10.3390/cancers13051103 · Cited by 100 · see citing works
Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies
Gu, D., Tang, H., Wu, J., Li, J., & Miao, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01049-7 · Cited by 99 · see citing works
Liclican, A. C., Serafini, L., Xing, W., Czerwieniec, G. A., Steiner, B. H., Wang, T., Brendza, K. M., Lutz, J. D., Keegan, K. S., Ray, A. S., et al. (2020) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2020.129531 · Cited by 98 · see citing works
Hutcheson, J., Vanarsa, K., Bashmakov, A., Grewal, S., Sajitharan, D., Chang, B. Y., Buggy, J. J., Zhou, X. J., Du, Y., Satterthwaite, A. B., et al. (2012) · Arthritis Research & Therapy · doi:10.1186/ar4086 · Cited by 96 · see citing works
Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis
Whang, J. A., & Chang, B. Y. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.028 · Cited by 95 · see citing works
Exploring the target scope of KEAP1 E3 ligase-based PROTACs
Du, G., Jiang, J., Henning, N. J., Safaee, N., Koide, E., Nowak, R. P., Donovan, K. A., Yoon, H., You, I., Yue, H., et al. (2022) · Cell chemical biology · doi:10.1016/j.chembiol.2022.08.003 · Cited by 94 · see citing works
Liu, L., Paolo, J. A. D., Barbosa, J., Rong, H., Reif, K., & Wong, H. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.181545 · Cited by 89 · see citing works
Self-citationLou, Y. C., Owens, T. D., Kuglstatter, A., Kondru, R. K., & GOLDSTEIN, D. M. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300035p · Cited by 88 · see citing works
Yu, J., Chen, L., Cui, B., Wu, C. C. N., Choi, M. Y., Chen, Y., Zhang, L., Rassenti, L. Z., Widhopf, G. F., & Kipps, T. J. (2016) · Leukemia · doi:10.1038/leu.2016.368 · Cited by 87 · see citing works
7-Azaindole: A Versatile Scaffold for Developing Kinase Inhibitors
Irie, T., & Sawa, M. (2017) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.c17-00380 · Cited by 87 · see citing works
Cuozzo, J. W., Gikunju, D., Habeshian, S., Hupp, C. D., Keefe, A. D., Sigel, E. A., Soutter, H. H., Thomson, H. A., Zhang, Y., & Clark, M. (2017) · ChemBioChem · doi:10.1002/cbic.201600573 · Cited by 81 · see citing works
Estupiñán, H. Y., Wang, Q., Berglöf, A., Schaafsma, G. C. P., Shi, Y., Zhou, L., Mohammad, D. K., Yu, L., Vihinen, M., Zain, R., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01123-6 · Cited by 80 · see citing works
Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies
Neys, S. F. H., Hendriks, R. W., & Corneth, O. B. J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.668131 · Cited by 80 · see citing works
BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses
Althubiti, M., Rada, M., Samuel, J., Escorsa, J. M., Najeeb, H., Lee, K.-G., Lam, K., Jones, G. D. D., Barlev, N. A., & Macip, S. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0690 · Cited by 76 · see citing works
Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma
Wu, H., Wang, W., Liu, F., Weisberg, E., Tian, B., Chen, Y., Li, B., Wang, A., Wang, B., Zhao, Z., et al. (2014) · ACS Chemical Biology · doi:10.1021/cb4008524 · Cited by 76 · see citing works
Review of the development of BTK inhibitors in overcoming the clinical limitations of ibrutinib
Ran, F., Liu, Y., Wang, C., Xu, Z., Zhang, Y., Liu, Y., Zhao, G., & Ling, Y. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114009 · Cited by 74 · see citing works
Robak, E., & Robak, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11102807 · Cited by 75 · see citing works
Bruton Tyrosine Kinase Is a Therapeutic Target in Stem-like Cells from Multiple Myeloma
Yang, Y., Shi, J., Gu, Z., Salama, M. E., Das, S., Wendlandt, E. B., Xu, H., Huang, J., Yi, T., Hao, M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2362 · Cited by 75 · see citing works
Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton’s Tyrosine Kinase
Smith, C. R., Dougan, D. R., Komandla, M., Kanouni, T., Knight, B., Lawson, J. D., Sabat, M. P., Taylor, E. R., Vu, P. H., & Wyrick, C. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00734 · Cited by 75 · see citing works
Liu, L., Halladay, J. S., Shin, Y. G., Wong, S., Coraggio, M., La, H., Baumgardner, M., Le, H. T., Gopaul, S. V., Boggs, J. W., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.040840 · Cited by 74 · see citing works
Self-citationRecent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases
Zhang, D., He, G., & Meng, F. (2021) · Molecules · doi:10.3390/molecules26164907 · Cited by 74 · see citing works
The Development of BTK Inhibitors: A Five-Year Update
Tasso, B., Spallarossa, A., Russo, E., & Brullo, C. (2021) · Molecules · doi:10.3390/molecules26237411 · Cited by 73 · see citing works
Tec Family Kinases in Inflammation and Disease
Horwood, N. J., Urbaniak, A. M., & Danks, L. (2012) · International Reviews of Immunology · doi:10.3109/08830185.2012.670334 · Cited by 73 · see citing works
Tyrosine Kinase Btk Is Required for NK Cell Activation
Bao, Y., Zheng, J. H., Han, C., Jin, J., Han, H., Liu, Y., Lau, Y., Tu, W., & Cao, X. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.372425 · Cited by 73 · see citing works
Katewa, A., Wang, Y., Hackney, J. A., Huang, T., Suto, E., Ramamoorthi, N., Austin, C. D., Bremer, M. C. D., Chen, J. Z., Crawford, J. J., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.90111 · Cited by 72 · see citing works
Self-citationStructural mechanism for Bruton’s tyrosine kinase activation at the cell membrane
Wang, Q., Pechersky, Y., Sagawa, S., Pan, A. C., & Shaw, D. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1819301116 · Cited by 72 · see citing works
Emerging small-molecule inhibitors of the Bruton’s tyrosine kinase (BTK): Current development
Liu, J., Chen, C., Wang, D., Zhang, J., & Zhang, T. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113329 · Cited by 71 · see citing works
Self-citationBODIPY catalyzed amide synthesis promoted by BHT and air under visible light
Wang, X., Yu, S.-S., Wang, C., Xue, D. Q., & Xiao, J. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c6ob00736h · Cited by 71 · see citing works
Puri, K. D., Paolo, J. A. D., & Gold, M. R. (2013) · International Reviews of Immunology · doi:10.3109/08830185.2013.818140 · Cited by 69 · see citing works
Ren, L., Campbell, A. R., Fang, H., Gautam, S., Elavazhagan, S., Fatehchand, K., Mehta, P., Stiff, A. R., Reader, B. F., Mo, X. M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.687251 · Cited by 69 · see citing works
Potent and selective Bruton’s tyrosine kinase inhibitors: Discovery of GDC-0834
Young, W. B., Barbosa, J., Blomgren, P., Bremer, M. C. D., Crawford, J. J., Dambach, D. M., Gallion, S., Hymowitz, S. G., Kropf, J. E., Lee, S., et al. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.01.032 · Cited by 68 · see citing works
Self-citationPark, J. K., Byun, J., Park, J. A., Kim, Y.-Y., Lee, Y. J., Oh, J. I., Jang, S. Y., Kim, Y., Song, Y. W., Son, J., et al. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-0988-z · Cited by 68 · see citing works
Medicinal Chemistry Strategies for the Development of Kinase Inhibitors Targeting Point Mutations
Lu, X., Smaill, J. B., & Ding, K. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00507 · Cited by 67 · see citing works
Targeting the SYK–BTK axis for the treatment of immunological and hematological disorders
Tan, S., Liao, C., Lucas, M. C., Stevenson, C. S., & DeMartino, J. A. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.02.001 · Cited by 64 · see citing works
Li, X., Zuo, Y., Tang, G., Wang, Y., Zhou, Y., Wang, X., Guo, T., Xia, M., Ding, N., & Pan, Z. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4017762 · Cited by 64 · see citing works
Cinnoline Scaffold—A Molecular Heart of Medicinal Chemistry?
Szumilak, M., & Stańczak, A. (2019) · Molecules · doi:10.3390/molecules24122271 · Cited by 63 · see citing works
Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., El‐Sherbeeny, A. M., Alasmari, A. F., Alanazi, W. A., Alasmari, F. F., Ibrahim, K. E., Al‐Harbi, M. M., Bakheet, S. A., et al. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106215 · Cited by 63 · see citing works
Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis
Kim, K., Maderna, A., Schnute, M. E., Hegen, M., Mohan, S., Miyashiro, J. S., Lin, L., Li, E., Keegan, S., Lussier, J., et al. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.09.008 · Cited by 63 · see citing works
Targeting B cells in treatment of autoimmunity
Franks, S. E., Getahun, A., Hogarth, P. M., & Cambier, J. C. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.09.003 · Cited by 61 · see citing works
Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease
Bam, R., Ling, W., Khan, S., Pennisi, A., Venkateshaiah, S. U., Li, X., van Rhee, F., Usmani, S. Z., Barlogie, B., Shaughnessy, J. D., et al. (2013) · American Journal of Hematology · doi:10.1002/ajh.23433 · Cited by 61 · see citing works
Montillo, M., O'Brien, S. M., Tedeschi, A., Byrd, J. C., Dearden, C. E., Gill, D. S., Brown, J. R., Barrientos, J. C., Mulligan, S. P., Furman, R. R., et al. (2017) · Blood Cancer Journal · doi:10.1038/bcj.2017.5 · Cited by 61 · see citing works
Al-Harbi, N. O., Nadeem, A., Ahmad, S. F., Bakheet, S. A., El‐Sherbeeny, A. M., Ibrahim, K. E., Alzahrani, K. S., Al‐Harbi, M. M., Mahmood, H. M., Alqahtani, F., et al. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173088 · Cited by 60 · see citing works
Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells
Hasan, M. K., Yu, J., Chen, L., Cui, B., Widhopf, G. F., Rassenti, L. Z., Shen, Z., Briggs, S. P., & Kipps, T. J. (2017) · Leukemia · doi:10.1038/leu.2017.133 · Cited by 60 · see citing works
Gillooly, K. M., Pulicicchio, C. M., Pattoli, M. A., Cheng, L., Skala, S., Heimrich, E., McIntyre, K. W., Taylor, T. L., Kukral, D. W., Dudhgaonkar, S. P., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181782 · Cited by 59 · see citing works
Inhibition of Bruton´s tyrosine kinase as a novel therapeutic approach in multiple sclerosis
Torke, S., & Weber, M. S. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1807934 · Cited by 57 · see citing works
A Fast and Clean BTK Inhibitor
Gabizon, R., & London, N. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00597 · Cited by 56 · see citing works
Bruton’s Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease
Neys, S. F. H., Rip, J., Hendriks, R. W., & Corneth, O. B. J. (2021) · Drugs · doi:10.1007/s40265-021-01592-0 · Cited by 58 · see citing works
Bruton's Tyrosine Kinase Inhibitors Prevent Therapeutic Escape in Breast Cancer Cells
Wang, X., Wong, J., Sevinsky, C. J., Kokabee, L., Khan, F., Sun, Y., & Conklin, D. S. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0813 · Cited by 55 · see citing works
Emerging nanotherapeutics alleviating rheumatoid arthritis by readjusting the seeds and soils
Zhang, W., Chen, Y., Liu, Q., Zhou, M. L., Wang, K., Wang, Y., Nie, J., Gui, S., Peng, D., He, Z., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.04.001 · Cited by 54 · see citing works
New Btk inhibitor holds promise
Hendriks, R. W. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.502 · Cited by 54 · see citing works
Corneth, O. B. J., de Bruijn, M. J. W., Rip, J., Asmawidjaja, P. S., Kil, L. P., & Hendriks, R. W. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600208 · Cited by 53 · see citing works
Marron, T. U., Martínez‐Gallo, M., Yu, J. E., & Cunningham‐Rundles, C. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.10.009 · Cited by 52 · see citing works
- Authors
- Di Paolo, J. A., Huang, T., Balazs, M., Barbosa, J., Barck, K. H., Bravo, B. J., Carano, R. A. D., Darrow, J., Davies, D. R., DeForge, L. E., Diehl, L., Ferrando, R., Gallion, S. L., Giannetti, A. M., Gribling, P., Hurez, V., Hymowitz, S. G., Jones, R., Kropf, J. E., Lee, W. P., Maciejewski, P. M., Mitchell, S. A., Rong, H., Staker, B. L., Whitney, J. A., Yeh, S., Young, W. B., Yu, C., Zhang, J., Reif, K., & Currie, K. S.
- Affiliations
- Genentech (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Reif, Karin
- Currie, Kevin S
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2010-11-28
- Volume
- 7
- Issue
- 1
- Pages
- 41-50
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2093522627
- Cited by
- 340
- References
- 50
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 13 · 2023: 14 · 2022: 26 · 2021: 35 · 2020: 29 · 2019: 25 · 2018: 22 · 2017: 33 · 2016: 22 · 2015: 26 · 2014: 23 · 2013: 16 · 2012: 15
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Genentech
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Bruton's tyrosine kinase, BTK inhibition, rheumatoid arthritis, inflammatory arthritis, B cell receptor signaling, FcγRIII, macrophage cytokine production, TNF-α, IL-1β, interleukin-6, B cell proliferation, collagen-induced arthritis
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Animals, Arthritis, Experimental, Arthritis, Rheumatoid, Autoantibodies, B-Lymphocytes, Benzamides, Enzyme Activation, Phosphorylation, Protein-Tyrosine Kinases, Tumor Necrosis Factor-alpha, Interleukin-6, Bridged Bicyclo Compounds, Heterocyclic, Myeloid Cells, Protein Kinase Inhibitors, Cell Proliferation, Mice, Interleukin-1beta
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