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AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients
Published version of a preprint
Abstract
AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib. AC0010 selectively inhibits EGFR-active and T790M mutations with up to 298-fold increase in potency compared with wild-type EGFR. In a xenograft model, oral administration of AC0010 at a daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR-active and T790M mutations for over 143 days with no weight loss. Three major metabolites of AC0010 were tested and showed no wild-type EGFR inhibition or off-target effects, such as inhibition of IGF-1R. AC0010 is safe in non–small cell lung cancer (NSCLC) patients at a dose range between 50 and 550 mg once per day, and no hyperglycemia or other severe adverse effects were detected, such as grade 3 QT prolongation. The objective responses were observed in NSCLC patients with EGFR T790M mutation. Mol Cancer Ther; 15(11); 2586–97. ©2016 AACR.
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“Moreover, the IC50 for EGFRL858R/T790M double mutant was 0.18 nM.159,160”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [159]
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Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., et al. (2007) · Nature · doi:10.1038/nature05945 · Cited by 5,439
Mitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70364-x · Cited by 4,090
Comprehensive genomic characterization of squamous cell lung cancers
The Cancer Genome Atlas Research Network (2012) · Nature · doi:10.1038/nature11404 · Cited by 3,994
EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527 · cited 4×
“Respiratory, thoracic, and mediastinal disorders Cough 1(25) 0 (0) 2(40) 0 (0) 2(29) 0 (0) 0 (0) 0 (0) 2(33) 0 (0) 7 (28) 0 (0) Haemoptysis 1(25) 0 (0) 2(40) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 3 (12) 0 (0)”
BackgroundInfluentialYu, 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
Herbst, R. S., Heymach, J. V., & Lippman, S. M. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0802714 · Cited by 2,435
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Research works printed but not linked: 2
- Simmons, 2015, Insulin-like growth factor 1 (IGF1R)/insulin receptor (INSR) inhibitory activity of rociletinib (CO-1686) and its metabolites in nonclinical models, Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, 18
- Haringsma, 2015, In vivo acquired resistance to the mutant EGFR inhibitor rociletinib (CO-1686) is associated with activation of the c-MET pathway, 18
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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
Nagasaka, M., Zhu, V. W., Lim, S. M., Greco, M., Wu, F., & Ou, S.-H. I. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.11.028 · Cited by 219
Lu, X., Yu, L., Zhang, Z., Ren, X., Smaill, J. B., & Ding, K. (2018) · Medicinal Research Reviews · doi:10.1002/med.21488 · Cited by 173
Han, L., Zhang, X., Wang, Z., Zhang, X., Zhao, L., Fu, W., Liang, X., Zhang, Z., & Wang, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.665253 · Cited by 31
Self-citationOvercoming Resistance to AC0010, a Third Generation of EGFR Inhibitor, by Targeting c-MET and BCL-2
Xu, W., Tang, W., Li, T., Zhang, X., & Sun, Y. (2019) · Neoplasia · doi:10.1016/j.neo.2018.11.004 · Cited by 23
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Metadata
- Authors
- Xu, X., Mao, L., Xu, W., Tang, W., Zhang, X., Xi, B., Xu, R., Fang, X., Liu, J., Fang, C., Zhao, L., Wang, X., Jiang, J., Hu, P., Zhao, H., & Zhang, L.
- Affiliations
- ACEA Biosciences (United States) (US)
- 1ACEA Pharmaceutical Research, Hangzhou, Zhejiang, P.R. China.
- Peking Union Medical College Hospital (CN)
- Sun Yat-sen University (CN)
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2016-11-01
- Volume
- 15
- Issue
- 11
- Pages
- 2586-2597
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- OpenAlex
- W2513491150
- Cited by
- 87
- References
- 30
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 12 · 2022: 7 · 2021: 14 · 2020: 13 · 2019: 9 · 2018: 13 · 2017: 6
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Twelfth Five-Year Plan (2013ZX09401003)
- Hangzhou Municipal (014-1249)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- irreversible EGFR inhibitors, pyrrolopyrimidine, T790M mutation, non-small cell lung cancer, EGFR mutation, drug resistance, xenograft models, drug metabolites, drug safety, oral administration
- MeSH terms
- Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Disease Models, Animal, Female, Humans, Lung Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Models, Molecular, Molecular Conformation, Mutation, Neoplasm Staging, Protein Binding, Treatment Outcome, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, ErbB Receptors
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