International Journal of New Chemistry
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A New Survey on the mTOR Inhibitors as Cancer Chemopreventive Agents

Document Type : Review

Authors

Rana Shirpour 1
Zahra Heidari 1
Kimia Noorali 1
Aliparsa Piramoun 1
Kimia Amirali 1
Maryam Bayanati 2
Mohammad Mahboubi-Rabbani 1

1 Department of Pharmaceutical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Department of Food Technology Research, National Nutrition, and Food Technology Research Institute/Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10.22034/ijnc.2025.723437
Abstract
The mammalian target of rapamycin (mTOR) pathway, which is critical for regulating cellular processes such as growth, metabolism, and survival, plays an important role in cancer development when dysregulated. mTOR inhibitors, notably rapamycin and its variants, have emerged as promising possibilities for cancer treatment and chemoprevention. This study focuses on the chemical characteristics of mTOR inhibitors and their potential utility in cancer chemoprevention. We investigate mTOR's function in cancer, assess the chemical structures of first- and second-generation mTOR inhibitors, describe their mode of action, and review preclinical and clinical data. In addition, we look at novel natural product-based inhibitors, dual inhibitors that target both PI3K and mTOR, and the hurdles of bringing these inhibitors to clinical usage.

Keywords

Mammalian Target of Rapamycin
mTOR
Cancer
Natural Product
Cancer Chemopreventive

Subjects

1          Laplante, M. & Sabatini, D. M. cell 149, 274 (2012).
2          Saxton, R. A. & Sabatini, D. M. Cell 168, 960 (2017).
3          Zoncu, R., Efeyan, A. & Sabatini, D. M. Nature reviews Molecular cell biology 12, 21 (2011).
4          Sarbassov, D. D., Guertin, D. A., Ali, S. M. & Sabatini, D. M. Science 307, 1098 (2005).
5          O'Reilly, K. E. et al. Cancer research 66, 1500 (2006).
6          Pópulo, H., Lopes, J. M. & Soares, P. International journal of molecular sciences 13, 1886 (2012).
7          Sehgal, S. in Transplantation proceedings.  S7 (Elsevier).
8          Houghton, P. & Huang, S. TOR: Target of Rapamycin, 339 (2004).
9          Faivre, S., Kroemer, G. & Raymond, E. Nature reviews Drug discovery 5, 671 (2006).
10        Benjamin, D., Colombi, M., Moroni, C. & Hall, M. N. Nature reviews Drug discovery 10, 868 (2011).
11        Janes, M. R. et al. Leukemia 27, 586 (2013).
12        Maira, S.-M. et al. Molecular cancer therapeutics 7, 1851 (2008).
13        Liu, Q., Thoreen, C., Wang, J., Sabatini, D. & Gray, N. S. Drug Discovery Today: Therapeutic Strategies 6, 47 (2009).
14        Hu, T.-h. et al. Cancer letters 354, 417 (2014).
15        Deng, L. et al. Acta Pharmacologica Sinica 38, 382 (2017).
16        Johnson, J. J. & Mukhtar, H. Cancer letters 255, 170 (2007).
17        Van Aller, G. S. et al. Biochemical and biophysical research communications 406, 194 (2011).
18        Alayev, A., Berger, S. M. & Holz, M. K. Annals of the New York Academy of Sciences 1348, 116 (2015).
International Journal of New Chemistry
Volume 12, Issue 5
Spring 2025
Pages 1036-1045

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