Metabolic disposition of the EGFR covalent inhibitor furmonertinib in humans
Open accessAbstract
Furmonertinib was designed for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. In this study, we investigated the metabolic disposition and mass balance in humans and tissue distribution in rats. After a single oral administration of 97.9 μCi/81.5 mg [14 C]-furmonertinib mesylate to six healthy male volunteers, the absorption process of furmonertinib was fast with a t max of total plasma radioactivity at 0.75 h. Afterward, furmonertinib was extensively metabolized, with the parent drug and active metabolite AST5902 accounting for 1.68% and 0.97% of total radioactivity in plasma. The terminal t 1/2 of total radioactivity in plasma was as long as 333 h, suggesting that the covalent binding of drug-related substances to plasma proteins was irreversible to a great extent. The most abundant metabolites identified in feces were desmethyl metabolite (AST5902), cysteine conjugate (M19), and parent drug (M0), which accounted for 6.28%, 5.52%, and 1.38% of the dose, respectively. After intragastric administration of 124 μCi/9.93 mg/kg [14 C]-furmonertinib to rats, drug-related substances were widely and rapidly distributed in tissues within 4 h. The concentration of total radioactivity in the lung was 100-fold higher than that in rat plasma, which could be beneficial to the treatment of lung cancer. Mass balance in humans was achieved with 77.8% of the administered dose recovered in excretions within 35 days after administration, including 6.63% and 71.2% in urine and feces, respectively. In conclusion, [14 C]-furmonertinib is completely absorbed and rapidly distributed into lung tissue, extensively metabolized in humans, presented mostly as covalent conjugates in plasma, and slowly eliminated mostly via fecal route.
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This enhances alflutinib's activity and kinase selectivity while reducing off-target effects, leading to fewer side effects.
“This enhances alflutinib’s activity and kinase selectivity while reducing off-target effects, leading to fewer side effects.146–148”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [146]
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Osimertinib or Platinum–Pemetrexed in <i>EGFR</i> T790M–Positive Lung Cancer
Mok, T. S., Wu, Y.-L., Ahn, M.-J., Garassino, M. C., Kim, H. R., Ramalingam, S. S., Shepherd, F. A., He, Y., Akamatsu, H., Theelen, W. S. M. E., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1612674 · Cited by 3,379 · see citing works
Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454 · see citing works
The resurgence of covalent drugs
Singh, J., Petter, R. C., Baillie, T. A., & Whitty, A. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3410 · Cited by 1,873 · see citing works
Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer
Mok, T. S. K., Wu, Y.-L. L. C., Ahn, M.-J., Garassino, M. C., Kim, H. R., Ramalingam, S., Shepherd, F. A., He, Y.-M., Akamatsu, H., Theelen, W. S. M. E., et al. (2017) · QUT ePrints (Queensland University of Technology) · Cited by 463 · see citing works
Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer
Wang, S., Cang, S., & Liu, D. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0268-z · Cited by 302 · see citing works
Murtuza, A., Bulbul, A., Shen, J. P., Keshavarzian, P., Woodward, B. D., Lopez-Diaz, F. J., Lippman, S. M., & Husain, H. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-1281 · Cited by 226 · see citing works
Olmutinib: First Global Approval
Kim, E. S. (2016) · Drugs · doi:10.1007/s40265-016-0606-z · Cited by 170 · see citing works
Scheers, E. M., Leclercq, L., de Jong, J., Bode, N., Bockx, M., Laenen, A., Cuyckens, F., Skee, D. M., Murphy, J., Sukbuntherng, J., et al. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.060061 · Cited by 143 · see citing works
Dickinson, P. A., Cantarini, M., Collier, J., Frewer, P., Martin, S. W., Pickup, K., & Ballard, P. G. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.069203 · Cited by 137 · see citing works
Shi, Y., Zhang, S., Hu, X., Feng, J., Ma, Z., Zhou, J., Yang, N., Wu, L., Liao, W., Zhong, D., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.01.010 · Cited by 111 · see citing works
Self-citationCharacterization of HKI-272 Covalent Binding to Human Serum Albumin
Wang, J., Li-Chan, X. X., Atherton, J., Deng, L., Espina, R. J., Yu, L., Horwatt, P., Ross, S. A., Lockhead, S., Ahmad, S. S., et al. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.032292 · Cited by 61 · see citing works
Graham, R., Lum, B. L., Morrison, G., Chang, I., Jorga, K. M., Dean, B., Shin, Y. G., Yue, Q., Mulder, T., Malhi, V., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.039339 · Cited by 58 · see citing works
Meng, J., Liu, X.-Y., Ma, S., Zhang, H., Yu, S.-D., Zhang, Y.-F., Chen, M.-X., Zhu, X.-Y., Liu, Y., Yi, L., et al. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0176-6 · Cited by 41 · see citing works
Self-citationCharacterization of covalent binding of tyrosine kinase inhibitors to plasma proteins
Liu, X., Feng, D., Zheng, M., Cui, Y., & Zhong, D. (2020) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2020.07.002 · Cited by 32 · see citing works
Self-citationAlflutinib (AST2818), primarily metabolized by CYP3A4, is a potent CYP3A4 inducer
Liu, X., Guo, Z., Chen, Z., Zhang, Y., Zhou, J., Jiang, Y., Zhao, Q., Diao, X., & Zhong, D. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0389-3 · Cited by 30 · see citing works
Self-citationHan, W., & Du, Y. (2017) · Chemistry & Biodiversity · doi:10.1002/cbdv.201600372 · Cited by 24 · see citing works
Liu, X., Li, W., Zhang, Y., Jiang, Y., Zhao, Q., & Zhong, D. (2019) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2019.06.032 · Cited by 16 · see citing works
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Cited by
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Deeks, E. D. (2021) · Drugs · doi:10.1007/s40265-021-01588-w · Cited by 55 · see citing works
Covalent Binding Mechanism of Furmonertinib and Osimertinib With Human Serum Albumin
Wu, Y., Chen, L., Chen, J., Xue, H., He, Q., Zhong, D., & Diao, X. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.001019 · Cited by 21 · see citing works
Self-citationDing, J., Ding, X., Zeng, J., & Liu, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1357913 · Cited by 21 · see citing works
Self-citationZou, H., Zhang, Y., Zhong, D., Jiang, Y., Liu, F., Zhao, Q., Zuo, Z., Zhang, Y., & Yan, X. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00798-y · Cited by 11 · see citing works
Self-citationBian, Y., Meng, J., Ma, S., Li, G., Wang, Y., Li, S., Liu, L., Huang, C., Zhang, H., Zhong, D., et al. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15256 · Cited by 8 · see citing works
Self-citationZhang, X., Han, H., Zhao, J., Liu, X., Zhang, J., Sun, R., Li, S., Liu, B., Zhu, H., Jiao, S., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.964606 · Cited by 8 · see citing works
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Yuan, C. (2025) · American Journal of Cancer Research · doi:10.62347/wtmu5537 · Cited by 8 · see citing works
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Al-Harthi, S., Alshehri, A., Alhudhali, L., Alghrably, M., Bennici, G., Almohaywi, M., Jaremko, Ł., & Jaremko, M. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1011323 · Cited by 4 · see citing works
Wong, S. G. W., & Ma, S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-817134-9.00004-0 · Cited by 4 · see citing works
Liu, D., Li, Q., Yan, S., Zhang, X., Li, W., Wang, F., Gao, L., Geng, F., Zhou, H., Ye, P., et al. (2025) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-024-04744-7 · Cited by 2 · see citing works
Pan, Y., Li, M., Yu, M., Chen, J., Yu, H., Liu, K., & Chen, L. (2025) · Translational Oncology · doi:10.1016/j.tranon.2025.102500 · Cited by 2 · see citing works
Zhang, K., Ge, Y., Xu, Y., Zhang, C., & Wang, L. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07114-w · Cited by 2 · see citing works
Lin, H., Yang, Z., Li, Z., Chen, J., Wang, H., & Lin, Y. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1321587 · Cited by 2 · see citing works
Leptomeningeal Disease in Lung Cancer: An Unmet Need That Needs to Be Met
Borghaei, H., & Mok, T. S. K. (2025) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2024.10.019 · Cited by 2 · see citing works
Guided Sample Pooling in Human Mass Balance Studies: A Recommended Strategic Decision Framework
Cuyckens, F., Li, W. ‐., Auclair, A., Cassidy, K. C., Cantalloube, C., Collins, G. W., James, A. D., Gibson, C. R., Glaenzel, U., Huth, F., et al. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.70157 · Cited by 1 · see citing works
DMPK Considerations for the Development of Covalent Drugs: Insights from an IQ Assessment
Dopstadt, J., Behnia, K., Cui, X., Colclough, N., Dowty, M. E., Enoru, J. O., Foti, R., Huth, F., Jacobs, F., Jamwal, R., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00214 · Cited by 1 · see citing works
Zheng, Y., Lu, X., Dong, H., Li, J., Shen, Y., Liu, Z., & Cui, H. (2025) · Oncology Letters · doi:10.3892/ol.2025.15074
Wu, Y., Loer, H. L. H., Zhang, Y., Zhong, D., Jiang, Y., Hu, J., Fuhr, U., Lehr, T., & Diao, X. (2025) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.70052
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Zhang, Y., Wang, D., Ma, H., & Wang, X. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1709552
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Zayed, M. F. (2026) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575451047260306044852
Yan, H., Jiang, W., 熊艺, Liu, L., Zhang, R., Ruan, Z., Huang, Z., Dai, J., Tian, F., Zhou, C., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102904
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- Authors
- Meng, J., Zhang, H., Bao, J.-J., Chen, Z.-D., Liu, X.-Y., Zhang, Y.-F., Jiang, Y., Miao, L.-Y., & Zhong, D.-F.
- Affiliations
- Chinese Academy of Sciences (CN)
- First Affiliated Hospital of Soochow University (CN)
- Venue
- Acta Pharmacologica Sinica
- Published
- 2021-04-29
- Volume
- 43
- Issue
- 2
- Pages
- 494-503
- ISSN
- 0253-9756 (ISSN-L)
- 1671-4083
- 1745-7254
- PMC
- PMC8791928
- OpenAlex
- W3157551671
- Cited by
- 23
- References
- 17
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Pharmacologica Sinica (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81521005)
- Chinese Academy of Sciences (XDA12050306)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- furmonertinib, drug metabolism, mass balance, tissue distribution, non-small cell lung cancer, T790M mutation, plasma protein binding, cysteine conjugates, fecal excretion, pharmacokinetics
- MeSH terms
- Administration, Oral, Adult, Animals, Antineoplastic Agents, Chromatography, High Pressure Liquid, Female, Humans, Indoles, Male, Pyridines, Pyrimidines, Tissue Distribution, Rats, Sprague-Dawley, Rats, ErbB Receptors
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