The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Conformational Control Inhibition of the BCR-ABL1 Tyrosine Kinase, Including the Gatekeeper T315I Mutant, by the Switch-Control Inhibitor DCC-2036
Open accessAbstract
Summary Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for chronic myeloid leukemia (CML) patients. Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead “switch-control” inhibitor, DCC-2036, potently inhibits both unphosphorylated and phosphorylated ABL1 by inducing a type II inactive conformation, and retains efficacy against the majority of clinically relevant CML resistance mutants, including T315I. DCC-2036 inhibits BCR-ABL1T315I-expressing cell lines, prolongs survival in mouse models of T315I-mutant CML and B-lymphoblastic leukemia, and inhibits primary patient leukemia cells expressing T315I in vitro and in vivo, supporting its clinical development in TKI-resistant Ph+ leukemia.
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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 2×
“Mutation of gatekeeper residues in epidermal growth factor receptor and c-KIT also leads to resistance to TKIs, including gefitinib and erlotinib in lung cancer (Pao et al., 2005), and imatinib in gastrointestinal stromal tumors (Wardelmann et al., 2005).”
BackgroundO'Brien, J., Wilson, I., Orton, T., & Pognan, F. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01606.x · Cited by 3,446
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001) · Science · doi:10.1126/science.1062538 · Cited by 3,104
Cited by
Sun, H., Li, Y., Shen, M., Tian, S., Xu, L., Pan, P., Guan, Y., & Hou, T. (2014) · Phys. Chem. Chem. Phys. · doi:10.1039/c4cp03179b · Cited by 526
Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy
Rossari, F., Minutolo, F., & Orciuolo, E. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0624-2 · Cited by 371
KLIFS: A Knowledge-Based Structural Database To Navigate Kinase–Ligand Interaction Space
van Linden, O. P. J., Kooistra, A. J., Leurs, R., de Esch, I. J. P., & de Graaf, C. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm400378w · Cited by 298
Conformational states dynamically populated by a kinase determine its function
Xie, T., Saleh, T., Rossi, P., & Kalodimos, C. G. (2020) · Science · doi:10.1126/science.abc2754 · Cited by 266
Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation
Pemovska, T., Johnson, E., Kontro, M., Repasky, G. A., Chen, J., Wells, P., Cronin, C. N., McTigue, M., Kallioniemi, O., Porkka, K., et al. (2015) · Nature · doi:10.1038/nature14119 · Cited by 234
Metadata
- Authors
- Chan, W. W., Wise, S. C., Kaufman, M. D., Ahn, Y. M., Ensinger, C. L., Haack, T., Hood, M. M., Jones, J., Lord, J. W., Lu, W. P., Miller, D., Patt, W. C., Smith, B. D., Petillo, P. A., Rutkoski, T. J., Telikepalli, H., Vogeti, L., Yao, T., Chun, L., Clark, R., Evangelista, P., Gavrilescu, L. C., Lazarides, K., Zaleskas, V. M., Stewart, L. J., Van Etten, R. A., & Flynn, D. L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 19
- Issue
- 4
- Pages
- 556-568
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2170527434
- Cited by
- 208
- References
- 3
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Chan, W. W., Wise, S. C., Kaufman, M. D., Ahn, Y. M., Ensinger, C. L., Haack, T., Hood, M. M., Jones, J., Lord, J. W., Lu, W. P., Miller, D., Patt, W. C., Smith, B. D., Petillo, P. A., Rutkoski, T. J., Telikepalli, H., Vogeti, L., Yao, T., Chun, L., . . . Flynn, D. L. (2011). Conformational Control Inhibition of the BCR-ABL1 Tyrosine Kinase, Including the Gatekeeper T315I Mutant, by the Switch-Control Inhibitor DCC-2036. Cancer Cell. https://doi.org/10.1016/j.ccr.2011.03.003
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
