A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas
Open accessPublished version of a preprint
Abstract
Purpose: Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Experimental Design: Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2–related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. Results: The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Conclusions: Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. Clin Cancer Res; 18(12); 3396–406. ©2012 AACR.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In another Phase I trial of CDDO-Me in patients with advanced solid tumors and lymphomas, a complete tumor response occurred in one mantle cell lymphoma patient and a partial response was observed in an anaplastic thyroid carcinoma patient at a dose of 900 mg/day.
“In another Phase I trial of CDDO-Me in patients with advanced solid tumors and lymphomas, a complete tumor response occurred in one mantle cell lymphoma patient and a partial response was observed in an anaplastic thyroid carcinoma patient at a dose of 900 mg/day.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredCDDO-Me has nonlinear dose-dependent exposures at high doses (600-1300 mg/day).
“Pharmacokinetic parameters suggest that CDDO-Me has a slow and saturable oral absorption, long terminal-phase half-life (39 hours at 900 mg/day), nonlinear dose-dependent exposures at high doses (600–1300 mg/day), and high interpatient variability.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
CDDO-Me has high interpatient variability.
“Pharmacokinetic parameters suggest that CDDO-Me has a slow and saturable oral absorption, long terminal-phase half-life (39 hours at 900 mg/day), nonlinear dose-dependent exposures at high doses (600–1300 mg/day), and high interpatient variability.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
The overall data appeared encouraging enough to support continued development of other synthetic triterpenoids as anticancer agents.
“Overall, the data appeared encouraging enough to support continued development of other synthetic triterpenoids as anticancer agents (Hong et al., 2012).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
CDDO-Me has a slow and saturable oral absorption.
“Pharmacokinetic parameters suggest that CDDO-Me has a slow and saturable oral absorption, long terminal-phase half-life (39 hours at 900 mg/day), nonlinear dose-dependent exposures at high doses (600–1300 mg/day), and high interpatient variability.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
CDDO-Me has a long terminal-phase half-life (39 hours at 900 mg/day).
“Pharmacokinetic parameters suggest that CDDO-Me has a slow and saturable oral absorption, long terminal-phase half-life (39 hours at 900 mg/day), nonlinear dose-dependent exposures at high doses (600–1300 mg/day), and high interpatient variability.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
Dose-limiting toxicities of CDDO-Me were grade 3 liver transaminase elevations that were reversible.
“Dose-limiting toxicities were grade 3 liver transaminase elevations that were reversible.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
In clinical trials, CDDO-Me showed therapeutic activities against several types of cancers.
“In clinical trials, CDDO-Me showed therapeutic activities against several types of cancers.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hong et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
Cheson, B. D., Horning, S., Coiffier, B., Shipp, M., Fisher, R. I., Connors, J. M., Lister, T., Vose, J., Grillo-López, A., Hagenbeek, A., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.4.1244 · Cited by 3,210 · see citing works
Bioanalytical Method Validation—A Revisit with a Decade of Progress
Shah, V. P., Midha, K. K., Findlay, J. W. A., Hill, H. M., Hulse, J. D., McGilveray, I. J., McKay, G., Miller, K. J., Patnaik, R. N., Powell, M. L., et al. (2000) · Pharmaceutical Research · doi:10.1023/a:1007669411738 · Cited by 1,574 · see citing works
Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes
Pergola, P. E., Raskin, P., Toto, R. D., Meyer, C. J., Huff, J. W., Grossman, E. B., Krauth, M., Ruiz, S., Audhya, P., Christ-Schmidt, H., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105351 · Cited by 890 · see citing works
Self-citationMalhotra, D., Portales-Casamar, É., Singh, A., Srivastava, S., Arenillas, D. J., Happel, C., Shyr, C., Wakabayashi, N., Kensler, T. W., Wasserman, W. W., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq212 · Cited by 796 · see citing works
Activation of Nrf2-antioxidant signaling attenuates NFκB-inflammatory response and elicits apoptosis
Li, W., Khor, T. O., Xu, C., Shen, G., Jeong, W.-S., Yu, S., & Kong, A.-N. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.07.017 · Cited by 738 · see citing works
Dinkova‐Kostova, A. T., Liby, K. T., Stephenson, K. K., Holtzclaw, W. D., Gao, X., Suh, N., Williams, C. R., Risingsong, R., Honda, T., Gribble, G. W., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500815102 · Cited by 575 · see citing works
Pueyo, M. E., Gonzalez, W., Nicoletti, A., Savoie, F., Arnal, J., & Michel, J. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.3.645 · Cited by 516 · see citing works
Oxidative Stress Is Progressively Enhanced With Advancing Stages of CKD
Dounousi, E. C., Papavasiliou, E. C., Makedou, A., Ioannou, K. I., Katopodis, K. P., Tselepis, A. D., Siamopoulos, K. C., & Tsakiris, D. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.08.015 · Cited by 412 · see citing works
Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide
Thimmulappa, R. K., Scollick, C., Traore, K., Yates, M. S., Trush, M. A., Liby, K. T., Sporn, M. B., Yamamoto, M. P., Kensler, T. W., & Biswal, S. S. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.102 · Cited by 356 · see citing works
Suh, N., Honda, T., Finlay, H. J., Barchowsky, A., Williams, C. R., Benoit, N. E., Xie, Q. W., Nathan, C., Gribble, G. W., & Sporn, M. B. (1998) · PubMed · Cited by 324 · see citing works
Nagaraj, S., Youn, J., Weber, H., Iclozan, C., Lu, L. D., Cotter, M. J., Meyer, C. J., Becerra, C. R., Fishman, M., Antonia, S. J., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3272 · Cited by 286 · see citing works
Self-citationTriterpenoid CDDO-Me Blocks the NF-κB Pathway by Direct Inhibition of IKKβ on Cys-179
Ahmad, R., Raina, D. B., Meyer, C. J., Kharbanda, S. M., & Kufe, D. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607160200 · Cited by 238 · see citing works
Self-citationEffect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b–4 CKD
Pérgola, P. E., Krauth, M., Huff, J. W., Ferguson, D. A., Ruiz, S., Meyer, C. J., & Warnock, D. G. (2011) · American Journal of Nephrology · doi:10.1159/000327599 · Cited by 232 · see citing works
Self-citationMyeloid-Derived Suppressor Cells in Human Cancer
Nagaraj, S., & Gabrilovich, D. I. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eb3358 · Cited by 222 · see citing works
Fernández, V., Hartmann, E., Ott, G., Campo, E., & Rosenwald, A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.019 · Cited by 211 · see citing works
Konopleva, M. Y., Tsao, T., Ruvolo, P. P., Stiouf, I., Estrov, Z. E., Leysath, C. E., Zhao, S., Harris, D., Chang, S., Jackson, C. E., et al. (2002) · Blood · doi:10.1182/blood.v99.1.326 · Cited by 189 · see citing works
Self-citationZhang, Y.-K. J., Yeager, R. L., Tanaka, Y., & Klaassen, C. D. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.03.016 · Cited by 170 · see citing works
Zou, W., Liu, X., Yue, P., Zhou, Z., Sporn, M. B., Lotan, R., Khuri, F. R., & Sun, S. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1238 · Cited by 167 · see citing works
Wu, Q., Wang, Y., Senitko, M., Meyer, C. J., Wigley, W. C., Ferguson, D. A., Grossman, E. B., Chen, J., Zhou, X. J., Hartono, J. R., et al. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00353.2010 · Cited by 158 · see citing works
Self-citationOsburn, W. O., Yates, M. S., Dolan, P. D., Chen, S., Liby, K. T., Sporn, M. B., Taguchi, K., Yamamoto, M. P., & Kensler, T. W. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn079 · Cited by 158 · see citing works
Shishodia, S., Sethi, G., Konopleva, M. Y., Andreeff, M., & Aggarwal, B. B. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2044 · Cited by 148 · see citing works
Self-citationTumor iNOS predicts poor survival for stage III melanoma patients
Ekmekçioglu, S., Ellerhorst, J. A., Prieto, V. G., Johnson, M. M., Broemeling, L. D., & Grimm, E. A. (2006) · International Journal of Cancer · doi:10.1002/ijc.21767 · Cited by 135 · see citing works
Common noncompartmental pharmacokinetic variables: are they normally or log-normally distributed?
Lacey, L. F., Keene, O. N., Pritchard, J. F., & Bye, A. (1997) · Journal of Biopharmaceutical Statistics · doi:10.1080/10543409708835177 · Cited by 124 · see citing works
Role of NF-κB in thyroid cancer
Pacifico, F., & Leonardi, A. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.10.010 · Cited by 123 · see citing works
Ahmad, R., Raina, D., Meyer, C., & Kufe, D. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-3036 · Cited by 120 · see citing works
Self-citationRAGE, vascular tone and vascular disease
Farmer, D., & Kennedy, S. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.06.013 · Cited by 108 · see citing works
Oncogenic and Anti-apoptotic Activity of NF-κB in Human Thyroid Carcinomas
Pacifico, F., Mauro, C., Barone, C., Crescenzi, E., Mellone, S., Monaco, M., Chiappetta, G., Terrazzano, G., Liguoro, D., Vito, P., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403492200 · Cited by 102 · see citing works
Ling, X., Konopleva, M. Y., Zeng, Z., Ruvolo, V. R., Stephens, L. C., Schober, W. D., McQueen, T. J., Dietrich, M. F., Madden, T. L., & Andreeff, M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3629 · Cited by 90 · see citing works
Self-citationHayashi, H., Karasawa, R., In, H., Saitou, T., Ueno, M., Nishi, S., Suzuki, Y., Ogino, S., Maruyama, Y., Kouda, Y., et al. (1992) · Kidney International · doi:10.1038/ki.1992.117 · Cited by 88 · see citing works
Liby, K. T., Risingsong, R., Royce, D. B., Williams, C. R., Yore, M. M., Honda, T., Gribble, G. W., Lamph, W. W., Vannini, N., Sogno, I., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0040 · Cited by 77 · see citing works
Duan, Z., Ames, R. Y., Ryan, M. B., Hornicek, F. J., Mankin, H. J., & Seiden, M. V. (2008) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-008-0785-8 · Cited by 75 · see citing works
Kim, K. B., Lotan, R., Yue, P., Sporn, M. B., Suh, N., Gribble, G. W., Honda, T., Wu, G. S., Hong, W. K., & Sun, S. Y. (2002) · PubMed · Cited by 70 · see citing works
Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients
Cottone, S., Mulè, G., Guarneri, M., Palermo, A., Lorito, M. C., Riccobene, R., Arsena, R., Vaccaro, F., Vadalà, A., Nardi, E., et al. (2008) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfn489 · Cited by 68 · see citing works
Hyer, M. L., Shi, R., Krajewska, M., Meyer, C. J., Lebedeva, I. V., Fisher, P. B., & Reed, J. C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5759 · Cited by 60 · see citing works
Self-citationLiby, K. T., Risingsong, R., Royce, D. B., Williams, C. R., Ma, T., Yore, M. M., & Sporn, M. B. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-09-0085 · Cited by 57 · see citing works
Jin, W., Zhu, L., Guan, Q., Chen, G., Wang, Q. F., Yin, H. X., Hang, C. H., Shi, J. X., & Wang, H. D. (2008) · PubMed · Cited by 56 · see citing works
The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent
Vannini, N., Lorusso, G., Cammarota, R., Barberis, M. C. P., Noonan, D. M., Sporn, M. B., & Albini, A. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0451 · Cited by 56 · see citing works
NF-κB Mediates Mitogen-Activated Protein Kinase Pathway-Dependent iNOS Expression in Human Melanoma
Uffort, D. G., Grimm, E. A., & Ellerhorst, J. A. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.205 · Cited by 29 · see citing works
Angiotensin II-Induced Signaling Pathways in Diabetes
Marrero, M. B., Fulton, D. J., Stepp, D. W., & Stern, D. M. (2005) · Current Diabetes Reviews · doi:10.2174/1573399054022802 · Cited by 22 · see citing works
Flagged first, then by citations
3 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
NF-κB in biology and targeted therapy: new insights and translational implications
Guo, Q., Jin, Y., Chen, X., Ye, X., Shen, X., Lin, M., Zeng, C., Zhou, T., & Zhang, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01757-9 · Cited by 2,267 · see citing works
Molecular basis of the Keap1–Nrf2 system
Suzuki, T., & Yamamoto, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.006 · Cited by 995 · see citing works
Ruiz, S., Pérgola, P. E., Zager, R. A., & Vaziri, N. D. (2013) · Kidney International · doi:10.1038/ki.2012.439 · Cited by 722 · see citing works
Oxidant Mechanisms in Renal Injury and Disease
Ratliff, B. B., Abdulmahdi, W., Pawar, R. D., & Wolin, M. S. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6665 · Cited by 699 · see citing works
Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach
Cuadrado, A., Manda, G., Hassan, A., Alcaraz, M. J., Barbas, C., Daiber, A., Ghezzi, P., León, R., López, M. G., Oliva, B., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014753 · Cited by 632 · see citing works
NF‐κB signaling in inflammation and cancer
Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021) · MedComm · doi:10.1002/mco2.104 · Cited by 615 · see citing works
Moses, T., Papadopoulou, K. Κ., & Osbourn, A. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2014.953628 · Cited by 559 · see citing works
Liby, K. T., & Sporn, M. B. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.004846 · Cited by 410 · see citing works
Ayeleso, T. B., Matumba, M. G., & Mukwevho, E. (2017) · Molecules · doi:10.3390/molecules22111915 · Cited by 335 · see citing works
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
Shanmugam, M. K., Dai, X., Kumar, A. P., Tan, B. K. H., Sethi, G., & Bishayee, A. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.01.016 · Cited by 273 · see citing works
Oxidative stress and the role of redox signalling in chronic kidney disease
Kishi, S., Nagasu, H., Kidokoro, K., & Kashihara, N. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00775-0 · Cited by 283 · see citing works
Moses, T., Pollier, J., Thevelein, J. M., & Goossens, A. (2013) · New Phytologist · doi:10.1111/nph.12325 · Cited by 245 · see citing works
Zhou, S.-F., Wang, Y., Zhe, H., Yang, Y., & He, Z. (2014) · Drug Design Development and Therapy · doi:10.2147/dddt.s68872 · Cited by 230 · see citing works
Antioxidants in Translational Medicine
Schmidt, H. H. H. W., Stocker, R., Vollbracht, C., Paulsen, G., Riley, D. P., Daiber, A., & Cuadrado, A. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6393 · Cited by 231 · see citing works
Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives
Tănase, D. M., Gosav, E. M., Anton, M. I., Floria, M., Isac, P. N. S., Hurjui, L. L., Tărniceriu, C. C., Costea, C. F., Ciocoiu, M., & Rezuș, C. (2022) · Biomolecules · doi:10.3390/biom12091227 · Cited by 203 · see citing works
Role of Nrf2 in protection against acute kidney injury
Shelton, L. M., Park, B. K., & Copple, I. M. (2013) · Kidney International · doi:10.1038/ki.2013.248 · Cited by 201 · see citing works
Comprehensive analysis of loops at protein-protein interfaces for macrocycle design
Gavenonis, J., Sheneman, B. A., Siegert, T. R., Eshelman, M. R., & Kritzer, J. A. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1580 · Cited by 201 · see citing works
The KEAP1–NRF2 System as a Molecular Target of Cancer Treatment
Taguchi, K., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers13010046 · Cited by 195 · see citing works
Targeting the KEAP1-NRF2 system to prevent kidney disease progression
Nezu, M., Suzuki, N., & Yamamoto, M. (2017) · American Journal of Nephrology · doi:10.1159/000475890 · Cited by 3,447 · see citing works
Roles of Nrf2 in Protecting the Kidney from Oxidative Damage
Nezu, M., & Suzuki, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082951 · Cited by 180 · see citing works
Keap Calm, and Carry on Covalently
Wilson, A. J., Kerns, J. K., Callahan, J. F., & Moody, C. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400224q · Cited by 171 · see citing works
Therapeutic approaches to diabetic nephropathy—beyond the RAS
Fernández‐Fernández, B., Ortíz, A., Gómez‐Guerrero, C., & Egido, J. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.74 · Cited by 169 · see citing works
Targeting inflammation in diabetic nephropathy: a tale of hope
Moreno, J. A., Gómez‐Guerrero, C., Mas, S., Sanz, A. B., Lorenzo, Ó., Ruiz‐Ortega, M., Opazo-Ríos, L., Mezzano, S. A., & Egido, J. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1538352 · Cited by 170 · see citing works
Potential Applications of NRF2 Modulators in Cancer Therapy
Panieri, E., Djordjević, A. B., Telkoparan‐Akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A. S., Skaperda, Z., Tsatsakis, A. M., Wallace, D., Süzen, S., et al. (2020) · Antioxidants · doi:10.3390/antiox9030193 · Cited by 165 · see citing works
Effect of Redox Modulating NRF2 Activators on Chronic Kidney Disease
Choi, B.-H., Kang, K.-S., & Kwak, M. (2014) · Molecules · doi:10.3390/molecules190812727 · Cited by 159 · see citing works
Salvador, J. A. R., Leal, A. S., Valdeira, A. S. C., Gonçalves, B. M. F., Alho, D. P. S., Figueiredo, S. A. C., Silvestre, S., & Mendes, V. I. S. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.07.013 · Cited by 160 · see citing works
Biomarkers of NRF2 signalling: Current status and future challenges
Morgenstern, C., Lastres‐Becker, I., Demirdöğen, B. C., Costa, V. M., Daiber, A., Foresti, R., Motterlini, R., Kalyoncu, S., Arioz, B. I., Genç, Ş., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103134 · Cited by 152 · see citing works
Drug repurposing screens identify chemical entities for the development of COVID-19 interventions
Bakowski, M. A., Beutler, N., Wolff, K. C., Kirkpatrick, M. G., Chen, E., Nguyen, T.-T., Riva, L., Shaabani, N., Parren, M., Ricketts, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23328-0 · Cited by 140 · see citing works
Adelusi, T. I., Du, L., Meng, H., Zhou, X., Qian, X., Chowdhury, A., Sun, Y., Lü, Q., & Yin, X. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109732 · Cited by 133 · see citing works
Targeting inflammation: New therapeutic approaches in chronic kidney disease (CKD)
Impellizzeri, D., Esposito, E., Attley, J., & Cuzzocrea, S. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.02.007 · Cited by 126 · see citing works
Nrf2 in health and disease: current and future clinical implications
Al‐Sawaf, O., Clarner, T., Fragoulis, A., Kan, Y. W., Pufe, T., Streetz, K. L., & Wruck, C. J. (2015) · Clinical Science · doi:10.1042/cs20150436 · Cited by 125 · see citing works
Sánchez-Ortega, M., Carrera, A. C., & Garrido, A. (2021) · Cells · doi:10.3390/cells10081879 · Cited by 124 · see citing works
Staurengo‐Ferrari, L., Badaro‐Garcia, S., Hohmann, M. S., Manchope, M. F., Zaninelli, T. H., Casagrande, R., & Verri, W. A., Jr. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01536 · Cited by 121 · see citing works
Ren, Y., & Kinghorn, A. D. (2019) · Planta Medica · doi:10.1055/a-0832-2383 · Cited by 119 · see citing works
Parikh, N. R., Mandal, A., Bhatia, D., Siveen, K. S., Sethi, G., & Bishayee, A. (2014) · Phytochemistry Reviews · doi:10.1007/s11101-014-9337-5 · Cited by 117 · see citing works
Oleanolic acid derivatives for pharmaceutical use: a patent review
Lin, C., Wen, X., & Sun, H. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2016.1182988 · Cited by 108 · see citing works
Chartoumpekis, D. V., & Kensler, T. W. (2013) · Current Diabetes Reviews · doi:10.2174/1573399811309020005 · Cited by 104 · see citing works
Current Landscape of NRF2 Biomarkers in Clinical Trials
Yagishita, Y., Gatbonton-Schwager, T. N., McCallum, M. L., & Kensler, T. W. (2020) · Antioxidants · doi:10.3390/antiox9080716 · Cited by 104 · see citing works
RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity
Probst, B., Isaac, T., Lyndsey, M., Bumeister, R., Dulubova, I., Wigley, W. C., & Ferguson, D. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122942 · Cited by 103 · see citing works
Self-citationDesign and development of Nrf2 modulators for cancer chemoprevention and therapy: a review
Sova, M., & Saso, L. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s172612 · Cited by 102 · see citing works
Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications
Akter, S., Madhuvilakku, R., Kar, A. K., Nila, I. S., Liu, P., Inuzuka, H., Wei, W., & Hong, Y. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02583-x · Cited by 119 · see citing works
NF-κB role on tumor proliferation, migration, invasion and immune escape
Khan, A., Zhang, Y., Ma, N., Shi, J., & Hou, Y. (2024) · Cancer Gene Therapy · doi:10.1038/s41417-024-00811-6 · Cited by 101 · see citing works
Synthesis and anticancer activity of CDDO and CDDO-Me, two derivatives of natural triterpenoids
Borella, R., Forti, L., Gibellini, L., De Gaetano, A., De Biasi, S., Nasi, M., Cossarizza, A., & Pinti, M. (2019) · Molecules · doi:10.3390/molecules24224097 · Cited by 98 · see citing works
Bardoxolone methyl: drug development for diabetic kidney disease
Kanda, H., & Yamawaki, K. (2020) · Clinical and Experimental Nephrology · doi:10.1007/s10157-020-01917-5 · Cited by 93 · see citing works
Biochemical and cellular basis of oxidative stress: Implications for disease onset
Aramouni, K., Assaf, R., Shaito, A. A., Fardoun, M., Al‐Asmakh, M., Sahebkar, A., & Eid, A. H. (2023) · Journal of Cellular Physiology · doi:10.1002/jcp.31071 · Cited by 90 · see citing works
Saito, H. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.01.006 · Cited by 90 · see citing works
Hancock, R., Schaap, M., Pfister, H., & Wells, G. (2013) · Organic & Biomolecular Chemistry · doi:10.1039/c3ob40249e · Cited by 91 · see citing works
Combating oxidative stress in diabetic complications with Nrf2 activators: How much is too much?
Tan, S. M., & de Haan, J. B. (2014) · Redox Report · doi:10.1179/1351000214y.0000000087 · Cited by 86 · see citing works
Zhou, S., Wang, P., Qiao, Y., Ge, Y., Wang, Y., Quan, S., Yao, R., Zhuang, S., Wang, L. J., Du, Y., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015050565 · Cited by 82 · see citing works
Keap1/Nrf2/ARE redox-sensitive signaling system as a pharmacological target
Зенков, Н. К., Брониславовна, М. Е., & Tkachev, V. (2013) · Biochemistry (Moscow) · doi:10.1134/s0006297913010033 · Cited by 81 · see citing works
Triterpenoids as reversal agents for anticancer drug resistance treatment
Yan, X., Gong, L.-H., Zheng, F.-Y., Cheng, K., Chen, Z., & Shi, Z. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.07.018 · Cited by 80 · see citing works
Wang, Y., Zhe, H., & Zhao, R. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-30 · Cited by 80 · see citing works
Aminzadeh, M. A., Reisman, S. A., Vaziri, N. D., Khazaeli, M., Yuan, J. J., & Meyer, C. J. (2013) · Xenobiotica · doi:10.3109/00498254.2013.852705 · Cited by 79 · see citing works
Self-citationTriterpenoids: Structural diversity, biosynthetic pathway, and bioactivity
Sandeep, S., & Ghosh, S. (2020) · Studies in natural products chemistry · doi:10.1016/b978-0-12-819483-6.00012-6 · Cited by 76 · see citing works
Park, J.-S., Rustamov, N., & Roh, Y. (2023) · Antioxidants · doi:10.3390/antiox12111928 · Cited by 77 · see citing works
Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease
Sakashita, M., Tanaka, T., & Inagi, R. (2021) · Antioxidants · doi:10.3390/antiox10071143 · Cited by 74 · see citing works
Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness
Espinosa-Sánchez, A., Suárez-Martínez, E., Sánchez-Díaz, L., & Carnero, A. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01533 · Cited by 71 · see citing works
Oleanolic Acid Induces Autophagy and Apoptosis via the AMPK-mTOR Signaling Pathway in Colon Cancer
Hu, C., Cao, Y., Li, P., Tang, X., Yang, M., Gu, S., Xiong, K., Li, T. X., & Xiao, T. (2021) · Journal of Oncology · doi:10.1155/2021/8281718 · Cited by 72 · see citing works
Szczęsny-Małysiak, E., Stojak, M., Campagna, R., Grosicki, M., Jamrozik, M., Kaczara, P., & Chłopicki, S. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/4678252 · Cited by 70 · see citing works
Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls
Aranda‐Rivera, A. K., Cruz‐Gregorio, A., Pedraza‐Chaverrí, J., & Scholze, A. (2022) · Antioxidants · doi:10.3390/antiox11061112 · Cited by 70 · see citing works
Prasad, S., Yadav, V. R., Sung, B., Gupta, S. C., Tyagi, A. K., & Aggarwal, B. B. (2016) · Oncotarget · doi:10.18632/oncotarget.7537 · Cited by 70 · see citing works
A Strategy for the Convergent and Stereoselective Assembly of Polycyclic Molecules
Robinson, E. E., & Thomson, R. J. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b13234 · Cited by 69 · see citing works
Huerta, C., Jiang, X. J., Isaac, T., Bender, C. F., Ferguson, D. A., Probst, B., Swinger, K. K., Stoll, V. S., Thomas, P., Dulubova, I., et al. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.07.026 · Cited by 69 · see citing works
Self-citationProbst, B., Lyndsey, M., Isaac, T., Wigley, W. C., & Ferguson, D. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135257 · Cited by 69 · see citing works
Self-citationRole of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy
Cui, W., Min, X., Xu, X., Du, B., & Luo, P. (2017) · Journal of Diabetes Research · doi:10.1155/2017/3797802 · Cited by 67 · see citing works
Nrf2 in early vascular ageing: Calcification, senescence and therapy
Arefin, S., Buchanan, S. J., Hobson, S., Steinmetz, J. L., Alsalhi, S., Shiels, P. G., Kublickiene, K. R., & Stenvinkel, P. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.02.026 · Cited by 66 · see citing works
To, C., Ringelberg, C. S., Royce, D. B., Williams, C. R., Risingsong, R., Sporn, M. B., & Liby, K. T. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv061 · Cited by 64 · see citing works
Khoo, N. K. H., Li, L., Salvatore, S. R., Schopfer, F. J., & Freeman, B. Α. (2018) · Scientific Reports · doi:10.1038/s41598-018-20460-8 · Cited by 63 · see citing works
Nrf2 activator for the treatment of kidney diseases
Yamawaki, K., Kanda, H., & Shimazaki, R. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.09.030 · Cited by 62 · see citing works
Hatherell, S., Baltazar, M. T., Reynolds, J., Carmichael, P. L., Dent, M. P., Li, H., Ryder, S., White, A., Walker, P., & Middleton, A. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa054 · Cited by 63 · see citing works
NF-κB and mitochondria cross paths in cancer: mitochondrial metabolism and beyond
Capece, D., Verzella, D., Francesco, B. D., Alesse, E., Franzoso, G., & Zazzeroni, F. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.021 · Cited by 62 · see citing works
Golubnitschaja, O., Kapinová, A., Sargheini, N., Bojková, B., Kapalla, M., Heinrich, L., Gkika, E., & Kubatka, P. (2024) · The EPMA Journal · doi:10.1007/s13167-024-00358-4 · Cited by 59 · see citing works
Mendoza, E. N., Ciriolo, M. R., & Ciccarone, F. (2025) · Antioxidants · doi:10.3390/antiox14010094 · Cited by 62 · see citing works
Samsuzzaman, M., Uddin, M. S., Shah, M. A., & Mathew, B. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.05.041 · Cited by 58 · see citing works
Creelan, B., Gabrilovich, D. I., Gray, J. E., Williams, C. C., Tanvetyanon, T., Haura, E. B., Weber, J. S., Gibney, G. T., Markowitz, J., Proksch, J. W., et al. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s136992 · Cited by 58 · see citing works
Self-citationMitochondrial quality control proteases and their modulation for cancer therapy
Zhang, J., Qiao, W., & Luo, Y. (2022) · Medicinal Research Reviews · doi:10.1002/med.21929 · Cited by 56 · see citing works
Wong, M. H. L., Bryan, H. K., Copple, I. M., Jenkins, R. E., Chiu, P. H., Bibby, J., Berry, N. G., Kitteringham, N. R., Goldring, C. E., O’Neill, P. M., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01292 · Cited by 56 · see citing works
Chen, Z., Huang, K., Ling, Y., Goto, M., Duan, H., Tong, X., Liu, Y.-L., Cheng, Y., Morris-Natschke, S. L., Yang, P., et al. (2019) · Journal of Natural Products · doi:10.1021/acs.jnatprod.9b00659 · Cited by 56 · see citing works
Wang, X., Zhang, X., Li, P., Liu, Z., Yang, Y., He, Z., Dang, H., & Zhou, S. (2017) · PubMed Central · Cited by 54 · see citing works
Wei, G., Luan, W., Wang, S., Cui, S., Fengran, L., Liu, Y., Liu, Y., & Cheng, M. (2014) · Organic & Biomolecular Chemistry · doi:10.1039/c4ob01605j · Cited by 53 · see citing works
Nuclear factor erythroid 2-related factor 2 as a treatment target of kidney diseases
Ito, M., Tanaka, T., & Nangaku, M. (2019) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000556 · Cited by 53 · see citing works
Eat Your Broccoli: Oxidative Stress, NRF2, and Sulforaphane in Chronic Kidney Disease
Liebman, S. E., & Le, T. H. (2021) · Nutrients · doi:10.3390/nu13010266 · Cited by 52 · see citing works
Keap1-independent Nrf2 regulation: A novel therapeutic target for treating kidney disease
Zhang, J., Zhang, M., Tatar, M., & Gong, R. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103593 · Cited by 50 · see citing works
Khurana, N., Kim, H., Chandra, P. K., Talwar, S., Sharma, P., Abdel‐Mageed, A. B., Sikka, S. C., & Mondal, D. (2017) · Oncology Reports · doi:10.3892/or.2017.5932 · Cited by 50 · see citing works
Nrf2‐Mediated Ferroptosis Inhibition Exerts a Protective Effect on Acute‐on‐Chronic Liver Failure
Wu, J., Xue, R., Wu, M., Yin, X., Xie, B., & Meng, Q. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4505513 · Cited by 50 · see citing works
Recent advances in medicinal chemistry of oleanolic acid derivatives
Yang, Y., Dai, S., Deng, F.-H., Peng, L.-H., Li, C., & Pei, Y. (2022) · Phytochemistry · doi:10.1016/j.phytochem.2022.113397 · Cited by 48 · see citing works
Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress
Mutter, F., Park, B. K., & Copple, I. M. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150044 · Cited by 48 · see citing works
Recent advances in the chemistry and biology of oleanolic acid and its derivatives
Verma, N., Raghuvanshi, D. S., & Singh, R. V. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116619 · Cited by 47 · see citing works
Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model
Park, J. W., Han, C. R., Zhao, L., Willingham, M. C., & Cheng, S.-Y. (2015) · Endocrine Related Cancer · doi:10.1530/erc-15-0417 · Cited by 47 · see citing works
Early aging and premature vascular aging in chronic kidney disease
Tanrıöver, C., Copur, S., Mutlu, A., Peltek, İ. B., Galassi, A., Ciceri, P., Cozzolino, M. G., & Kanbay, M. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad076 · Cited by 44 · see citing works
Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis
Aihara, S., Torisu, K., Uchida, Y., Imazu, N., Nakano, T., & Kitazono, T. (2023) · Communications Biology · doi:10.1038/s42003-023-05057-w · Cited by 44 · see citing works
NRF2 in kidney physiology and disease
Bondi, C. D., Hartman, H. L., & Tan, R. J. (2024) · Physiological Reports · doi:10.14814/phy2.15961 · Cited by 45 · see citing works
Non-covalent NRF2 Activation Confers Greater Cellular Protection than Covalent Activation
Liu, P., Tian, W., Tao, S., Tillotson, J., Wijeratne, E. M. K., Gunatilaka, A. A. L., Zhang, D. D., & Chapman, E. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.07.011 · Cited by 44 · see citing works
Lamhamedi-Cherradi, S.-E., Menegaz, B. A., Ramamoorthy, V., Aiyer, R. A., Maywald, R. L., Buford, A. S., Doolittle, D. K., Culotta, K. S., O'Dorisio, J. E., & Ludwig, J. A. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0334 · Cited by 43 · see citing works
Liese, J., Abhari, B. A., & Fulda, S. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.04.018 · Cited by 41 · see citing works
Anaplastic Thyroid Cancer: Outcome and the Mutation/Expression Profiles of Potential Targets
Wu, H., Sun, Y., Ye, H., Yang, S., Lee, S. L., & Morenas, A. D. L. (2015) · Pathology & Oncology Research · doi:10.1007/s12253-014-9876-5 · Cited by 41 · see citing works
Oleanane derivatives for pharmaceutical use: A patent review (2000–2016)
Masullo, M., Pizza, C., & Piacente, S. (2017) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1253680 · Cited by 41 · see citing works
Gleixner, K. V., Schneeweiss‐Gleixner, M., Eisenwort, G., Berger, D., Herrmann, H., Blatt, K., Greiner, G., Byrgazov, K., Hoermann, G., Konopleva, M. Y., et al. (2017) · Haematologica · doi:10.3324/haematol.2016.163436 · Cited by 41 · see citing works
Self-citationZhou, S., Wang, Y., Yang, Y., He, Z., Zhao, R., Zhe, H., Zhang, X., Pan, S., Duan, W., Yang, T., et al. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s73493 · Cited by 39 · see citing works
- Authors
- Hong, D. S., Kurzrock, R., Supko, J. G., He, X., Naing, A., Wheler, J., Lawrence, D., Eder, J. P., Meyer, C. J., Ferguson, D. A., Mier, J., Konopleva, M., Konoplev, S., Andreeff, M., Kufe, D., Lazarus, H., Shapiro, G. I., & Dezube, B. J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Hong, David S.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2012-06-14
- Volume
- 18
- Issue
- 12
- Pages
- 3396-3406
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4494099
- OpenAlex
- W2087928294
- Cited by
- 236
- References
- 43
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 17 · 2023: 14 · 2022: 21 · 2021: 18 · 2020: 17 · 2019: 20 · 2018: 14 · 2017: 18 · 2016: 15 · 2015: 23 · 2014: 17 · 2013: 13 · 2012: 3
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA166480, R01CA042802, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- bardoxolone methyl, synthetic triterpenoids, Nrf2 activation, NF-κB inhibition, dose-limiting toxicity, maximum tolerated dose, pharmacokinetics, pharmacodynamics, NQO1, mantle cell lymphoma, anaplastic thyroid carcinoma, advanced solid tumors, anticancer activity, liver transaminase elevation, estimated glomerular filtration rate, chronic kidney disease, oral administration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Renal Cell, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Kidney Neoplasms, Lymphoma, Male, Melanoma, Middle Aged, Neoplasms, Oleanolic Acid, RNA, Messenger, Thyroid Neoplasms, Colorectal Neoplasms, NF-kappa B, NAD(P)H Dehydrogenase (Quinone), Cyclin D1, Maximum Tolerated Dose, STAT Transcription Factors, NF-E2-Related Factor 2, Janus Kinases, Young Adult
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
