The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia
Open accessAbstract
Mcl-1 is a member of the Bcl-2 family of proteins that promotes cell survival by preventing induction of apoptosis in many cancers. High expression of Mcl-1 causes tumorigenesis and resistance to anticancer therapies highlighting the potential of Mcl-1 inhibitors as anticancer drugs. Here, we describe AZD5991, a rationally designed macrocyclic molecule with high selectivity and affinity for Mcl-1 currently in clinical development. Our studies demonstrate that AZD5991 binds directly to Mcl-1 and induces rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia, by activating the Bak-dependent mitochondrial apoptotic pathway. AZD5991 shows potent antitumor activity in vivo with complete tumor regression in several models of multiple myeloma and acute myeloid leukemia after a single tolerated dose as monotherapy or in combination with bortezomib or venetoclax. Based on these promising data, a Phase I clinical trial has been launched for evaluation of AZD5991 in patients with hematological malignancies (NCT03218683).
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay
Molina, D. M., Jafari, R., Ignatushchenko, M., Seki, T., Larsson, E. A., Dan, C., Sreekumar, L., Cao, Y., & Nordlund, P. (2013) · Science · doi:10.1126/science.1233606 · Cited by 2,261
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
Roberts, A. W., Davids, M. S., Pagel, J. M., Kahl, B. S., Puvvada, S. D., Gerecitano, J. F., Kipps, T. J., Anderson, M. A., Brown, J. R., Gressick, L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1513257 · Cited by 1,900
Pan-cancer patterns of somatic copy number alteration
Zack, T. I., Schumacher, S. E., Carter, S. L., Cherniack, A. D., Saksena, G., Tabak, B., Lawrence, M. S., Zhang, C.-Z., Wala, J., Mermel, C. H., et al. (2013) · Nature Genetics · doi:10.1038/ng.2760 · Cited by 1,870
The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models
Kotschy, A., Szlavik, Z., Murray, J., Davidson, J., Maragno, A. L., Le Toumelin-Braizat, G., Chanrion, M., Kelly, G. L., Gong, J.-N., Moujalled, D. M., et al. (2016) · Nature · doi:10.1038/nature19830 · Cited by 1,047
Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
Wertz, I. E., Kusam, S., Lam, C., Okamoto, T., Sandoval, W., Anderson, D. J., Helgason, E., Ernst, J. A., Eby, M., Liu, J., et al. (2011) · Nature · doi:10.1038/nature09779 · Cited by 794
Davids, M. S., Roberts, A. W., Seymour, J. F., Pagel, J. M., Kahl, B. S., Wierda, W. G., Puvvada, S., Kipps, T. J., Anderson, M. A., Salem, A. H., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.70.4320 · Cited by 748
Hu, S., Xu-Monette, Z. Y., Tzankov, A., Green, T., Wu, L., Balasubramanyam, A., Liu, W.-M., Visco, C., Li, Y., Miranda, R. N., et al. (2013) · Blood · doi:10.1182/blood-2012-10-460063 · Cited by 679
Mcl‐1; the molecular regulation of protein function
Thomas, L. W., Lam, C., & Edwards, S. W. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.05.061 · Cited by 538
Wei, G., Twomey, D., Lamb, J., Schlis, K., Agarwal, J., Stam, R. W., Opferman, J. T., Sallan, S. E., den Boer, M. L., Pieters, R., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.09.006 · Cited by 509
Cited by
The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Vogler, M., Braun, Y., Smith, V. M., Westhoff, M.-A., Pereira, R. S., Pieper, N. M., Anders, M., Callens, M., Vervliet, T., Abbas, M., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02176-0 · Cited by 462
The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs
Diepstraten, S. T., Anderson, M. A., Czabotar, P. E., Lessene, G., Strasser, A., & Kelly, G. L. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00407-4 · Cited by 346
Basu, A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107943 · Cited by 171
Targeting MCL-1 protein to treat cancer: opportunities and challenges
Tantawy, S. I., Timofeeva, N., Sarkar, A., & Gandhi, V. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1226289 · Cited by 90
Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells
Lafontaine, J., Cardin, G. B., Malaquin, N., Boisvert, J.-S., Rodier, F., & Wong, P. (2021) · Cancers · doi:10.3390/cancers13030386 · Cited by 54
Metadata
- Authors
- Tron, A. E., Belmonte, M. A., Adam, A., Aquila, B. M., Boise, L. H., Chiarparin, E., Cidado, J., Embrey, K. J., Gangl, E., Gibbons, F. D., Gregory, G. P., Hargreaves, D., Hendricks, J. A., Johannes, J. W., Johnstone, R. W., Kazmirski, S. L., Kettle, J. G., Lamb, M. L., Matulis, S. M., Nooka, A. K., Packer, M. J., Peng, B., Rawlins, P. B., Robbins, D. W., Schuller, A. G., Su, N., Yang, W., Ye, Q., Zheng, X., Secrist, J. P., Clark, E. A., Wilson, D. M., Fawell, S. E., & Hird, A. W.
- Venue
- Nature Communications
- Published
- 2018-12-17
- Volume
- 9
- Issue
- 1
- Pages
- 5341-5341
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2905070646
- Cited by
- 490
- References
- 44
- FWCI
- 17.81
- Type
- journal article
- Language
- en
- Open access
- gold
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. https://app.cochat.ai/papers/10.1038/s41467-018-07551-w
- The paper
- Tron, A. E., Belmonte, M. A., Adam, A., Aquila, B. M., Boise, L. H., Chiarparin, E., Cidado, J., Embrey, K. J., Gangl, E., Gibbons, F. D., Gregory, G. P., Hargreaves, D., Hendricks, J. A., Johannes, J. W., Johnstone, R. W., Kazmirski, S. L., Kettle, J. G., Lamb, M. L., Matulis, S. M., . . . Hird, A. W. (2018). Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. Nature Communications. https://doi.org/10.1038/s41467-018-07551-w
Data sources
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.
