The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule
Open accessAbstract
Human pancreatic ductal adenocarcinoma (PDAC) involves the dysregulation of multiple signaling pathways. A novel approach to the treatment of PDAC is described, involving the targeting of cancer genes in PDAC pathways having over-representation of G-quadruplexes, using the trisubstituted naphthalene diimide quadruplex-binding compound 2,7-bis(3-morpholinopropyl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzo[ lmn][3,8]phenanthroline-1,3,6,8(2 H,7 H)-tetraone (CM03). This compound has been designed by computer modeling, is a potent inhibitor of cell growth in PDAC cell lines, and has anticancer activity in PDAC models, with a superior profile compared to gemcitabine, a commonly used therapy. Whole-transcriptome RNA-seq methodology has been used to analyze the effects of this quadruplex-binding small molecule on global gene expression. This has revealed the down-regulation of a large number of genes, rich in putative quadruplex elements and involved in essential pathways of PDAC survival, metastasis, and drug resistance. The changes produced by CM03 represent a global response to the complexity of human PDAC and may be applicable to other currently hard-to-treat cancers.
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Cites
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Cited by
The Structure and Function of DNA G-Quadruplexes
Spiegel, J., Adhikari, S., & Balasubramanian, S. (2020) · Trends in Chemistry · doi:10.1016/j.trechm.2019.07.002 · Cited by 920
“perspective, it is noteworthy that a G4 ligand that lacks traditional ‘drug-like’ properties has shown significant accumulation and efficacy in tumour xenografts of human cancers [29].”
BackgroundInfluentialSelf-citationG-quadruplexes: a promising target for cancer therapy
Kosiol, N., Juranek, S., Brossart, P., Heine, A., & Paeschke, K. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01328-4 · Cited by 533
Naphthalene diimides: perspectives and promise
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Ligands stimulating antitumour immunity as the next G-quadruplex challenge
Miglietta, G., Marinello, J., Russo, M., & Capranico, G. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01649-y · Cited by 44
“AQ1 • Oncogene targeting • Oncogenic cell death • Cell survival inhibition [30, 31]”
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Metadata
- Authors
- Marchetti, C., Zyner, K. G., Ohnmacht, S. A., Robson, M., Haider, S. M., Morton, J. P., Marsico, G., Vo, T., Laughlin-Toth, S., Ahmed, A. A., Di Vita, G., Pazitna, I., Gunaratnam, M., Besser, R. J., Andrade, A. C. G., Diocou, S., Pike, J. A., Tannahill, D., Pedley, R. B., Evans, T. R. J., Wilson, W. D., Balasubramanian, S., & Neidle, S.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-01-22
- Volume
- 61
- Issue
- 6
- Pages
- 2500-2517
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2784819782
- Cited by
- 166
- References
- 18
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Marchetti, C., Zyner, K. G., Ohnmacht, S. A., Robson, M., Haider, S. M., Morton, J. P., Marsico, G., Vo, T., Laughlin-Toth, S., Ahmed, A. A., Di Vita, G., Pazitna, I., Gunaratnam, M., Besser, R. J., Andrade, A. C. G., Diocou, S., Pike, J. A., Tannahill, D., Pedley, R. B., . . . Neidle, S. (2018). Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.7b01781
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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.
