Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis
Abstract
Autoantibody production and immune complex deposition within the kidney promote renal disease in patients with lupus nephritis. Thus, therapeutics that inhibit these pathways may be efficacious in the treatment of systemic lupus erythematosus. Bruton's tyrosine kinase (BTK) is a critical signaling component of both BCR and FcR signaling. We sought to assess the efficacy of inhibiting BTK in the development of lupus-like disease, and in this article describe (R)-5-amino-1-(1-cyanopiperidin-3-yl)-3-(4-[2,4-difluorophenoxy]phenyl)-1H-pyrazole-4-carboxamide (PF-06250112), a novel highly selective and potent BTK inhibitor. We demonstrate in vitro that PF-06250112 inhibits both BCR-mediated signaling and proliferation, as well as FcR-mediated activation. To assess the therapeutic impact of BTK inhibition, we treated aged NZBxW_F1 mice with PF-06250112 and demonstrate that PF-06250112 significantly limits the spontaneous accumulation of splenic germinal center B cells and plasma cells. Correspondingly, anti-dsDNA and autoantibody levels were reduced in a dose-dependent manner. Moreover, administration of PF-06250112 prevented the development of proteinuria and improved glomerular pathology scores in all treatment groups. Strikingly, this therapeutic effect could occur with only a modest reduction observed in anti-dsDNA titers, implying a critical role for BTK signaling in disease pathogenesis beyond inhibition of autoantibody production. We subsequently demonstrate that PF-06250112 prevents proteinuria in an FcR-dependent, Ab-mediated model of glomerulonephritis. Importantly, these results highlight that BTK inhibition potently limits the development of glomerulonephritis by impacting both cell- and effector molecule-mediated pathways. These data provide support for evaluating the efficacy of BTK inhibition in systemic lupus erythematosus patients.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies reported successful conversion of either a reversible ibrutinib scaffold or a different noncovalent analog derived from a previously published covalent BTK inhibitor into BTK degraders.
“Subsequently, several studies reported successful conversion of either a reversible ibrutinib scaffold 42,43 or a different noncovalent analog derived from a previously published covalent BTK inhibitor 44,45 into BTK degraders.”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [45]
Cites
Honigberg, L. A., Smith, A. M., Sirisawad, M., Verner, E., Loury, D., Chang, B., Li, S., Pan, Z., Thamm, D. H., Miller, R. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004594107 · Cited by 1,561 · see citing works
Murine Models of Systemic Lupus Erythematosus
Theofilopoulos, A. N., & Dixon, F. J. (1985) · Advances in immunology · doi:10.1016/s0065-2776(08)60342-9 · Cited by 1,553 · see citing works
Defective B cell development and function in Btk-deficient mice
Khan, W. N., Alt, F. W., Gerstein, R. M., Malynn, B. A., Larsson, I., Rathbun, G. A., Davidson, L., Müller, S., Kantor, A. B., Herzenberg, L. A., et al. (1995) · Immunity · doi:10.1016/1074-7613(95)90114-0 · Cited by 726 · see citing works
Chan, O. T. M., Hannum, L. G., Haberman, A. M., Madaio, M. P., & Shlomchik, M. J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.10.1639 · Cited by 698 · see citing works
Discovery of Selective Irreversible Inhibitors for Bruton’s Tyrosine Kinase
Pan, Z., Scheerens, H., Li, S., Schultz, B. E., Sprengeler, P. A., Burrill, L. C., Mendonca, R. V., Sweeney, M. D., Scott, K. C. K., Grothaus, P. G., et al. (2006) · ChemMedChem · doi:10.1002/cmdc.200600221 · Cited by 690 · see citing works
Uncoupling of Immune Complex Formation and Kidney Damage in Autoimmune Glomerulonephritis
Clynes, R., Dumitru, C. D., & Ravetch, J. V. (1998) · Science · doi:10.1126/science.279.5353.1052 · Cited by 621 · see citing works
T-Cell Signaling Regulated by the Tec Family Kinase, ItkPreprint
Andreotti, A. H., Schwartzberg, P. L., Joseph, R. E., & Berg, L. J. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002287 · Cited by 595 · see citing works
Fc‐Receptors as Regulators of Immunity
Nimmerjahn, F., & Ravetch, J. V. (2007) · Advances in immunology · doi:10.1016/s0065-2776(07)96005-8 · Cited by 419 · see citing works
Requirement for Tec Kinases Rlk and Itk in T Cell Receptor Signaling and Immunity
Schaeffer, E. M., Debnath, J., Yap, G. S., McVicar, D. W., Liao, X. C., Littman, D. R., Sher, A., VARMUS, H. E., Lenardo, M. J., & Schwartzberg, P. L. (1999) · Science · doi:10.1126/science.284.5414.638 · Cited by 398 · see citing works
The pathogenesis of systemic lupus erythematosus—an update
Choi, J.-Y., Kim, S. T., & Craft, J. E. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.10.004 · Cited by 360 · see citing works
Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis
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., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.481 · Cited by 340 · see citing works
Regulation of Btk Function by a Major Autophosphorylation Site Within the SH3 Domain
Park, H., Wahl, M. I., Afar, D., Turck, C. W., Rawlings, D. J., Tam, C. C., Scharenberg, A. M., Kinet, J., & Witte, O. N. (1996) · Immunity · doi:10.1016/s1074-7613(00)80417-3 · Cited by 323 · see citing works
Smith, C. I. E., Baskin, B., Humire-Greiff, P., Zhou, J., Olsson, P. G., Maniar, H. S., Kjellén, P., Lambris, J. D., Christensson, B., Hammarström, L. L. G., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.2.557 · Cited by 308 · see citing works
Raz, E., Brezis, M., Rosenmann, E., & Eilat, D. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.142.9.3076 · Cited by 270 · see citing works
Hata, D., Kawakami, Y., Inagaki, N., Lantz, C. S., Kitamura, T., Khan, W. N., Maeda‐Yamamoto, M., Miura, T., Han, W., Hartman, S. E., et al. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.8.1235 · Cited by 262 · see citing works
Liu, X., Zhan, Z., Li, D., Xu, L., Ma, F., Zhang, P., Yao, H., & Cao, X. (2011) · Nature Immunology · doi:10.1038/ni.2015 · Cited by 261 · see citing works
Activated Renal Macrophages Are Markers of Disease Onset and Disease Remission in Lupus Nephritis
Schiffer, L. E., Bethunaickan, R., Ramanujam, M., Huang, W., Schiffer, M., Tao, H., Madaio, M. P., Böttinger, E. P., & Davidson, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1938 · Cited by 229 · see citing works
Lupus nephritis: Correlation of interstitial cells with glomerular function
Alexopoulos, E., Serón, D., Hartley, R., & Cameron, J. S. (1990) · Kidney International · doi:10.1038/ki.1990.14 · Cited by 225 · see citing works
Kil, L. P., de Bruijn, M. J. W., van Nimwegen, M., Corneth, O. B. J., van Hamburg, J. P., Dingjan, G. M., Thaiss, F., Rimmelzwaan, G. F., Elewaut, D. S., Delsing, D. J. M., et al. (2012) · Blood · doi:10.1182/blood-2011-12-397919 · Cited by 210 · see citing works
Bruton's Tyrosine Kinase Links the B Cell Receptor to Nuclear Factor κb Activation
Bajpai, U. D., Zhang, K., Teutsch, M. R., Sen, R., & Wortis, H. H. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.10.1735 · Cited by 208 · see citing works
Moreth, K., Brodbeck, R., Babelova, A., Gretz, N., Spieker, T., Zeng-Brouwers, J., Pfeilschifter, J., Young, M. F., Schaefer, R. M., & Schaefer, L. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42213 · Cited by 207 · see citing works
Severe B Cell Deficiency in Mice Lacking the Tec Kinase Family Members Tec and Btk
Ellmeier, W., Jung, S., Sunshine, M. J., Hatam, F., Xu, Y., Baltimore, D., Mano, H., & Littman, D. R. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.11.1611 · Cited by 205 · see citing works
Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.
Biesecker, G., Katz, S. K., & Koffler, D. (1981) · The Journal of Experimental Medicine · doi:10.1084/jem.154.6.1779 · Cited by 193 · see citing works
Cheng, G., Ye, Z. S., & Baltimore, D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.8152 · Cited by 171 · see citing works
Local macrophage proliferation in human glomerulonephritis
Yang, N., Isbel, N. M., Nikolic‐Paterson, D. J., Li, Y., Rengao, Y., Atkins, R. C., & Lan, H. Y. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00978.x · Cited by 166 · see citing works
CTLA4Ig inhibits T cell–dependent B-cell maturation in murine systemic lupus erythematosus
Mihara, M., Tan, I. J., Chuzhin, Y., Reddy, B., Budhai, L., Holzer, A. M., Gu, Y., & Davidson, A. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9244 · Cited by 166 · see citing works
Ikezumi, Y., Hurst, L., Masaki, T., Atkins, R. C., & Nikolic‐Paterson, D. J. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00717.x · Cited by 157 · see citing works
Khan, S. B., Cook, H. T., Bhangal, G., Smith, J., Tam, F. W. K., & Pusey, C. D. (2005) · Kidney International · doi:10.1111/j.1523-1755.2005.00279.x · Cited by 145 · 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
Cutaneous Localization of the Membrane Attack Complex in Discoid and Systemic Lupus Erythematosus
Biesecker, G., Lavin, L., Ziskind, M., & Koffler, D. (1982) · New England Journal of Medicine · doi:10.1056/nejm198202043060503 · Cited by 139 · see citing works
Kurosaki, T., & Kurosaki, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.25.15595 · Cited by 133 · 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
Steinberg, B. J., Smathers, P. A., Frederiksen, K., & Steinberg, A. D. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110651 · Cited by 129 · 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
FcR-Bearing Myeloid Cells Are Responsible for Triggering Murine Lupus Nephritis
Bergtold, A., Gavhane, A., D’Agati, V. D., Madaio, M. P., & Clynes, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.10.7287 · Cited by 122 · 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
Immunoglobulin subclass-specific immunodeficiency in mice with an X-linked B-lymphocyte defect.
Perlmutter, R. M., Nahm, M. H., Stein, K. E., Slack, J. H., Zitron, I. M., Paul, W. E., & Davie, J. M. (1979) · The Journal of Experimental Medicine · doi:10.1084/jem.149.4.993 · Cited by 110 · 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
Btk dosage determines sensitivity to B cell antigen receptor cross-linking
Satterthwaite, A. B., Cheroutre, H., Khan, W. N., Sideras, P., & Witte, O. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13152 · Cited by 101 · see citing works
Bekar, K. W., Owen, T., Dunn, R., Ichikawa, T., Wang, W., Wang, R., Barnard, J., Brady, S. P., Nevarez, S., Goldman, B., et al. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27515 · Cited by 100 · see citing works
Rankin, A. L., Guay, H., Herber, D., Bertino, S. A., Duzanski, T. A., Carrier, Y., Keegan, S., Senices, M., Stedman, N., RYAN, M. S., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1003871 · Cited by 83 · see citing works
Mina‐Osorio, P., LaStant, J., Keirstead, N. D., Whittard, T., Ayala, J., Stefanova, S., Garrido, R., Dimaano, N. M., Hilton, H., Giron, M., et al. (2013) · Arthritis & Rheumatism · doi:10.1002/art.38047 · Cited by 82 · see citing works
Chemotactic Factor-induced Recruitment and Activation of Tec Family Kinases in Human Neutrophils
Lachance, G., Levasseur, S., & Naccache, P. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201903200 · Cited by 74 · see citing works
MacGlashan, D. W., Honigberg, L. A., Smith, A., Buggy, J. J., & Schroeder, J. T. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2010.12.018 · Cited by 74 · see citing works
Transgene Expression of bcl-xL Permits Anti-immunoglobulin (Ig)–induced Proliferation in xid B Cells
Solvason, N. W., Wu, W., Kabra, N. H., Lund‐Johansen, F., Roncarolo, M. G., Behrens, T. W., Grillot, D., Núñez, G., Lees, E. M., & Howard, M. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.7.1081 · Cited by 74 · see citing works
Lupus Serum IgG Induces Skin Inflammation through the TNFR1 Signaling Pathway
Deng, G., Liu, L., Kyttaris, V. C., & Tsokos, G. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902514 · Cited by 64 · see citing works
Fc receptor–independent development of autoimmune glomerulonephritis in lupus‐prone MRL/lpr mice
Matsumoto, K., Watanabe, N., Akikusa, B., Kurasawa, K., Matsumura, R., Saito, Y., Iwamoto, I., & Saito, T. (2003) · Arthritis & Rheumatism · doi:10.1002/art.10813 · Cited by 64 · see citing works
B Cell receptor directs the activation of NFAT and NF-κB via distinct molecular mechanisms
Antony, P., Petro, J. B., Carlesso, G., Shinners, N. P., Lowe, J. A., III, & Khan, W. N. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00338-0 · Cited by 57 · see citing works
Al, A., Kanegane, H., Miyawaki, T., & Mm, V. (2003) · PubMed · Cited by 54 · see citing works
Otten, M. A., Groeneveld, T. W. L., Flierman, R., Rastaldi, M. P., Trouw, L. A., Faber‐Krol, M. C., Visser, A., Essers, M. C., Claassens, J. W. C., Verbeek, J. S., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901301 · Cited by 46 · see citing works
Schiffer, L. E., Bethunaickan, R., Ramanujam, M., Huang, W., Schiffer, M., Tao, H., Madaio, M. P., Böttinger, E. P., & Davidson, A. (2008) · The Journal of Immunology · Cited by 26 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · 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
Neuropsychiatric lupus: new mechanistic insights and future treatment directions
Schwartz, N., Stock, A. D., & Putterman, C. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-018-0156-8 · Cited by 441 · see citing works
Delineating the role of cooperativity in the design of potent PROTACs for BTK
Zorba, A., Nguyen, C., Xu, Y., Starr, J., Borzilleri, K., Smith, J., Zhu, H., Farley, K. A., Ding, W., Schiemer, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803662115 · Cited by 419 · 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
The conneXion between sex and immune responses
Forsyth, K. S., Jiwrajka, N., Lovell, C. D., Toothacre, N. E., & Anguera, M. C. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-00996-9 · Cited by 226 · 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
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
New therapies for systemic lupus erythematosus — past imperfect, future tense
Murphy, G., & Isenberg, D. A. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0235-5 · Cited by 158 · 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
An update on lupus animal models
Li, W., Titov, A. A., & Morel, L. M. (2017) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000412 · Cited by 146 · see citing works
Efficacy 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
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
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
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
Julià, A., López-Longo, F. J., Venegas, J. J. P., Bonàs‐Guarch, S., Olivé, À., Andreu, J. L., Aguirre, M. A., Vela, P., Solé, J. M. N., de la Fuente, J. L. M., et al. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1604-1 · Cited by 108 · see citing works
Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol
Goedken, E. R., Argiriadi, M. A., Banach, D. L., Fiamengo, B. A., Foley, S. E., Frank, K. E., George, J. S., Harris, C. M., Hobson, A. D., Ihle, D. C., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.595181 · Cited by 101 · 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
Winkler, A. R., Sun, W., De, S., Jiao, A., Sharif, M., Symanowicz, P. T., Athale, S., Shin, J. H., Wang, J., Jacobson, B. A., et al. (2021) · Arthritis & Rheumatology · doi:10.1002/art.41953 · Cited by 93 · see citing works
Wang, X., Zhang, C., Wu, Z., Chen, Y., & Shi, W. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1618-8 · Cited by 86 · see citing works
Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors
Casimiro‐Garcia, A., Trujillo, J. I., Vajdos, F. F., Juba, B. M., Banker, M. E., AULABAUGH, A. E., Balbo, P., Bauman, J. N., Chrencik, J., Coe, J. W., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01308 · Cited by 84 · see citing works
Syrett, C. M., & Anguera, M. C. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.6ri0319-094r · Cited by 81 · see citing works
Price, E., Bombardieri, M., Kivitz, A., Matzkies, F., Gurtovaya, O., Pechonkina, A., Jiang, W., Downie, B., Mathur, A. N., Mozaffarian, A., et al. (2022) · Lara D. Veeken · doi:10.1093/rheumatology/keac167 · Cited by 80 · 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
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
Herman, A. E., Chinn, L. W., Kotwal, S. G., Murray, E. R., Zhao, R. Z., Florero, M., Lin, A., Moein, A., Wang, R., Bremer, M. C. D., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1056 · Cited by 68 · see citing works
Meant to B: B cells as a therapeutic target in systemic lupus erythematosus
Atisha‐Fregoso, Y., Toz, B., & Diamond, B. (2021) · Journal of Clinical Investigation · doi:10.1172/jci149095 · Cited by 65 · see citing works
High Accuracy Prediction of PROTAC Complex Structures
Ignatov, M., Jindal, A., Kotelnikov, S., Beglov, D., Posternak, G., Tang, X., Maisonneuve, P., Poda, G. I., Batey, R. A., Sicheri, F., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c09387 · Cited by 60 · see citing works
Jackson, S. W., Kolhatkar, N. S., & Rawlings, D. J. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.01.018 · 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
Lucca, G. V. D., Shi, Q., Liu, Q., Batt, D. G., Bertrand, M. B., Rampulla, R., Mathur, A., Discenza, L., D’Arienzo, C. J., Dai, J., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00722 · Cited by 57 · see citing works
Chalmers, S. A., Wen, J., Doerner, J., Stock, A. D., Cuda, C. M., Makinde, H. M., Perlman, H., Bosanac, T., Webb, D. S. A., Nabozny, G. H., et al. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1500-0 · 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
Btk inhibition treats TLR7/IFN driven murine lupus
Bender, A. T., Pereira, A., Fu, K., Samy, E. T., Wu, Y., Liu‐Bujalski, L., Caldwell, R. D., Chen, Y.-Y., Tian, H., Morandi, F., et al. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.01.012 · Cited by 52 · see citing works
Garg, N., Padron, E., Rammohan, K. W., & Goodman, C. F. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11206139 · Cited by 52 · see citing works
Kong, W., Deng, W., Sun, Y., Huang, S., Zhang, Z., Shi, B., Chen, W., Tang, X., Yao, G., Feng, X., et al. (2017) · Clinical Rheumatology · doi:10.1007/s10067-017-3717-3 · Cited by 49 · see citing works
The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies
Wang, Y., Xiao, S., Xia, Y., & Wang, H. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08898-7 · Cited by 46 · see citing works
B-Cell Receptor Signaling in Lymphoid Malignancies and Autoimmunity
Avalos, A. M., Meyer‐Wentrup, F. A. G., & Ploegh, H. L. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800266-7.00004-2 · Cited by 47 · see citing works
Satterthwaite, A. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01986 · Cited by 47 · see citing works
Vukelic, M., Li, Y., & Kyttaris, V. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02658 · Cited by 47 · see citing works
Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., Ibrahim, K. E., Alqahtani, F., Alanazi, W. A., Mahmood, H. M., Alsanea, S., & Attia, S. M. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107123 · Cited by 45 · see citing works
HM71224, a selective Bruton’s tyrosine kinase inhibitor, attenuates the development of murine lupus
Kim, Y.-Y., Park, K. T., Jang, S. Y., Lee, K. H., Byun, J., Suh, K. H., Lee, Y., Kim, Y., & Hwang, K. W. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1402-1 · Cited by 43 · see citing works
Lupus nephritis and B-cell targeting therapy
Cassia, M. A., Alberici, F., Gallieni, M. A., & Jayne, D. R. W. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1366855 · Cited by 41 · see citing works
Corzo, C. A., Varfolomeev, E. E., Setiadi, A., Francis, R., Klabunde, S., Senger, K., Sujatha-Bhaskar, S., Drobnick, J., Do, S., Suto, E., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz1053 · Cited by 41 · see citing works
Chalmers, S. A., Doerner, J., Bosanac, T., Khalil, S. D. S., Smith, D. M., Harcken, C., Dimock, J., Der, E. B., Herlitz, L., Webb, D. S. A., et al. (2016) · Scientific Reports · doi:10.1038/srep26164 · Cited by 40 · see citing works
Bruton’s Tyrosine Kinase Inhibitors: A New Therapeutic Target for the Treatment of SLE?
Lorenzo-Vizcaya, A. M., Fasano, S., & Isenberg, D. A. (2020) · ImmunoTargets and Therapy · doi:10.2147/itt.s240874 · Cited by 40 · see citing works
Bruton’s Tyrosine Kinase Inhibitors: Recent Updates
Fares, A. A., Uribe, C. R. C., Martinez, D., Rehman, T. U., Rondon, C. S., & Sandoval-Sus, J. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042208 · Cited by 39 · see citing works
From mechanism to therapies in systemic lupus erythematosus
Paley, M., Strand, V., & Kim, A. H. J. (2017) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000369 · Cited by 38 · see citing works
Future landscape for the management of membranous nephropathy
Caravaca‐Fontán, F., Yandián, F., & Fervenza, F. C. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad041 · Cited by 37 · see citing works
Modeling the Clinical Phenotype of BTK Inhibition in the Mature Murine Immune System
Benson, M. J., Rodriguez, V., von Schack, D., Keegan, S., Cook, T. A., Edmonds, J., Benoit, S., Seth, N. P., Du, S., Messing, D., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302570 · Cited by 32 · see citing works
Schnute, M. E., Benoit, S., Buchler, I. P., Caspers, N. L., Grapperhaus, M. L., Han, S., Hotchandani, R., Huang, N., Hughes, R. O., Juba, B. M., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00461 · Cited by 30 · see citing works
Yao, X. Y., Sun, X., Jin, S., Yang, L. L., Xu, H., & Rao, Y. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00329 · Cited by 30 · see citing works
Bame, E., Tang, H., Burns, J. C., Arefayene, M., Michelsen, K., Ma, B., Marx, I. E., Prince, R. J., Roach, A. M., Poreci, U., et al. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1295 · Cited by 30 · see citing works
Progress of small molecules for targeted protein degradation: PROTACs and other technologies
Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31 · see citing works
Ma, T. K.-W., McAdoo, S. P., & Tam, F. W. K. (2017) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfw336 · Cited by 30 · see citing works
Nyhoff, L. E., Barron, B. L., Johnson, E., Bonami, R. H., Maseda, D., Fensterheim, B. A., Han, W., Blackwell, T. S., Crofford, L. J., & Kendall, P. L. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39657 · Cited by 29 · see citing works
Bruton’s tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder
Liu, Y., Huang, Z., Zhang, T., Han, B., Yang, G., Jia, D., Yang, L., Liu, Q., Lau, A. Y. L., Paul, F., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02997-2 · Cited by 26 · see citing works
B Cell Aberrance in Lupus: the Ringleader and the Solution
Nie, Y., Zhao, L., & Zhang, X. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-020-08820-7 · Cited by 26 · see citing works
Therapeutic targeting of BET protein BRD4 delays murine lupus
Wei, S., Sun, Y., & Sha, H. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.10.036 · Cited by 26 · see citing works
Arthur, R., Valle‐Argos, B., Steele, A. J., & Packham, G. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00009 · Cited by 24 · see citing works
Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline
Mok, C. C. (2023) · Drugs · doi:10.1007/s40265-023-01856-x · Cited by 22 · see citing works
Wolska, A., & Smolewski, P. (2022) · Cancers · doi:10.3390/cancers14153778 · Cited by 21 · see citing works
The Immunomodulatory Mechanisms of BTK Inhibition in CLL and Beyond
Jiang, Q., Peng, Y., Herling, C., & Herling, M. (2024) · Cancers · doi:10.3390/cancers16213574 · Cited by 19 · see citing works
Biologic therapies for systemic lupus erythematosus: where are we now?
Murphy, G., & Isenberg, D. A. (2020) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000736 · Cited by 19 · see citing works
Current Status in the Discovery of Covalent Janus Kinase 3 (JAK3) Inhibitors
Dai, J., Yang, L., & Addison, G. (2019) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557519666190617152011 · Cited by 19 · see citing works
Crawford, J. J., Lee, W., Johnson, A. R., Delatorre, K. J., Chen, J., Eigenbrot, C. W., Heidmann, J. D., Kakiuchi-Kiyota, S., Katewa, A., Kiefer, J. R., et al. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00249 · Cited by 18 · see citing works
Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus
Meng, S., Li, T., Wang, T., Li, D., Chen, J., Li, H., Cai, W., Zeng, Z., Liu, D. J., Tang, D., et al. (2022) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2022.100434 · Cited by 14 · see citing works
Shinde, A., Panchal, K., Katke, S., Paliwal, R., & Chaurasiya, A. (2021) · Therapies · doi:10.1016/j.therap.2021.10.010 · Cited by 13 · see citing works
Liossis, S. C., & Μελισσαρόπουλος, Κ. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.894976 · Cited by 13 · see citing works
Du, Y., Lei, L., Ding, H., Chen, Y., Pathak, S., Hicks, J., Tran, P. T., Wu, M., Chang, B. Y., Wirtz, U., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.893899 · Cited by 13 · see citing works
Identification of candidate regulators of mandibular bone loss in FcγRIIB-/- Mice
Sakunrangsit, N., Pholtaisong, J., Sucharitakul, J., Wanna-udom, S., Prombutara, P., Pisitkun, P., Leelahavanichkul, A., Aporntewan, C., Greenblatt, M. B., & Lotinun, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-98108-3 · Cited by 11 · see citing works
Srivastava, A., Ko, S. S., Watterson, S. H., Pattoli, M. A., Skala, S., Cheng, L., Obermeier, M. T., Vickery, R., Discenza, L., D’Arienzo, C. J., et al. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00335 · Cited by 10 · see citing works
Guo, Y., Hu, N., Liu, Y., Zhang, W., Yu, D., Shi, G., Zhang, B., Yin, L., Wei, M., Yuan, X., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01938 · Cited by 8 · see citing works
Advances in therapeutic targets-related study on systemic lupus erythematosus.
Wang, X., Zhang, Q., Luo, S., Zhang, H., Lu, Q., & Long, H. (2021) · PubMed Central · doi:10.11817/j.issn.1672-7347.2021.200056 · Cited by 7 · see citing works
Chen, J.-S., Chang, L.-C., Huang, S.-J., & Cheng, C. (2014) · BioMed Research International · doi:10.1155/2014/814869 · Cited by 7 · see citing works
Delignat, S., Russick, J., Gangadharan, B., Rayes, J., Ing, M., Voorberg, J., Kaveri, S. V., & Lacroix‐Desmazes, S. (2018) · Haematologica · doi:10.3324/haematol.2018.200279 · Cited by 7 · see citing works
Litzenburger, T., Steffgen, J., Benediktus, E., Müller, F., Schultz, A., Klein, E. S., Ramanujam, M., Harcken, C., Gupta, A., Wu, J. T., et al. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14571 · Cited by 6 · see citing works
Kyttaris, V. C. (2017) · Current Rheumatology Reports · doi:10.1007/s11926-017-0638-8 · Cited by 5 · see citing works
Bruton’s Tyrosine Kinase (Btk) Inhibitor Tirabrutinib Prevents the Development of Murine Lupus
Ariza, Y., Murata, M., Ueda, Y., & Yoshizawa, T. (2019) · European Journal of Experimental Biology · doi:10.36648/2248-9215.9.1.79 · Cited by 5 · see citing works
Bruton's tyrosine kinase inhibition suppresses pathological retinal angiogenesis
Chen, S., Liu, Y., Zhang, Y., Guo, X., Bai, T., He, K., Zhu, Y. P., Yi, L., Du, M., Wang, X., et al. (2024) · British Journal of Pharmacology · doi:10.1111/bph.17344 · Cited by 5 · see citing works
Autoimmunity in Primary Immunodeficiency Disorders
Kitcharoensakkul, M., & Cooper, M. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812102-3.00028-2 · Cited by 5 · see citing works
Bruton’s tyrosine kinase in chronic inflammation: from pathophysiology to therapy
Reedquist, K. A., Hartkamp, L. M., & Radstake, T. R. D. J. (2015) · International Journal of Interferon Cytokine and Mediator Research · doi:10.2147/ijicmr.s71779 · Cited by 5 · see citing works
Enhanced Bruton’s tyrosine kinase activity in the kidney of patients with IgA nephropathy
Wei, J., Wang, Y., Qi, X., & Wu, Y. (2021) · International Urology and Nephrology · doi:10.1007/s11255-020-02733-2 · Cited by 5 · see citing works
Ding, B., Li, M., Liu, L., Song, X., Zhang, Y., Xia, A., Liu, J., & Zhou, H. (2025) · Cancer Reports · doi:10.1002/cnr2.70152 · Cited by 4 · see citing works
Joshi, D., Bahekar, R. H., Soman, S. S., Jadav, P., Patel, D. N., Goswami, A., Pethani, J. P., Kumar, J., Patel, J., Sundar, R., et al. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106238 · Cited by 4 · see citing works
Shi, X., Luo, C., Chen, Y., Hong, X., Liao, T., Peng, Y., Zheng, S. G., & Miao, Y. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115297 · Cited by 3 · see citing works
Khan, S. N., Han, P., Chaudhury, R., Bickerton, S., Lee, J. S., Calderon, B. M., Pellowe, A. S., Gonzalez, A. L., & Fahmy, T. M. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00836 · Cited by 3 · see citing works
Drug Repurposing Patent Applications April–June 2015
Mucke, H. A. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.29030.pq2 · Cited by 3 · see citing works
Evolution of Small-Molecule Immunology Research—Changes Since CMC II
Dhar, T. G. M., & Dyckman, A. J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12401-1 · Cited by 3 · see citing works
PROteolysis TArgetting Chimeras (PROTACs) Strategy Applied to Kinases: Recent Advances
Feral, A., Laconde, G., Amblard, M., & Masurier, N. (2020) · Advanced Therapeutics · doi:10.1002/adtp.202000148 · Cited by 3 · see citing works
Molecular therapeutic strategies in neurodegenerative diseases and injury
Tora, M. S., Texakalidis, P., Greven, A., Faraj, R. R., Gendreau, J. L., Liang, Z., Federici, T., & Boulis, N. M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818084-6.00012-x · Cited by 2 · see citing works
Chen, X., Huang, Y., Xu, W., Cai, Y., & Yang, Y. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00139j · Cited by 2 · see citing works
Parker, J. T., Chang, C.-Y., Kersjes, K., Higgins, I. A., Vendel, A. C., & Chang, W. Y. (2024) · Biology · doi:10.3390/biology13100778 · Cited by 1 · see citing works
Choi, K. J., Kim, Y.-Y., Jang, S. Y., Ahn, Y., Suh, K. H., Kim, Y., & Kim, H. S. (2021) · In Vivo · doi:10.21873/invivo.12619 · Cited by 1 · see citing works
Drug Repurposing Patent Applications April–June 2016
Mucke, H. A. (2016) · Assay and Drug Development Technologies · doi:10.1089/adt.2016.29052.pq2 · Cited by 1 · see citing works
- Authors
- Rankin, A. L., Seth, N., Keegan, S., Andreyeva, T., Cook, T. A., Edmonds, J., Mathialagan, N., Benson, M. J., Syed, J., Zhan, Y., Benoit, S. E., Miyashiro, J. S., Wood, N., Mohan, S., Peeva, E., Ramaiah, S. K., Messing, D., Homer, B. L., Dunussi-Joannopoulos, K., Nickerson-Nutter, C. L., Schnute, M. E., & Douhan, J.
- Affiliations
- Pfizer (United States) (US)
- Immunoscience, Pfizer Research , Cambridge, MA 02140
- Corresponding author
- Seth, Nilufer
- Keegan, Sean
- Andreyeva, Tatyana
- Edmonds, Jason
- Wood, Nancy
- Mohan, Shashi
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-11-01
- Volume
- 191
- Issue
- 9
- Pages
- 4540-4550
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2163431182
- Cited by
- 113
- References
- 52
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 15 · 2019: 9 · 2018: 17 · 2017: 10 · 2016: 11 · 2015: 6 · 2014: 7
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- Bruton's tyrosine kinase, BTK inhibition, systemic lupus erythematosus, lupus nephritis, autoantibody production, anti-dsDNA antibodies, B cell receptor signaling, Fc receptor signaling, germinal center B cells, plasma cells, proteinuria, NZB/W F1 mice, autoimmunity
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Animals, B-Lymphocytes, Disease Models, Animal, Female, Glomerulonephritis, Kidney, Lupus Erythematosus, Systemic, Lymphocyte Activation, Mice, Inbred NZB, Piperidines, Plasma Cells, Protein-Tyrosine Kinases, Pyrazoles, Receptors, Fc, T-Lymphocytes, Signal Transduction, Germinal Center, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
