A comprehensive review on phosphatidylinositol-3-kinase (PI3K) and its inhibitors bearing pyrazole or indazole core for cancer therapy.

Autor: Bastos IM; LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal., Rebelo S; Institute of Biomedicine-iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal., Silva VLM; LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address: verasilva@ua.pt.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Aug 01; Vol. 398, pp. 111073. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.cbi.2024.111073
Abstrakt: Cancer is a complex and multifaceted group of diseases with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. Dysregulation of normal signalling pathways in cancer contributes to the different hallmarks of this disease. The signalling pathway of which phosphatidylinositol 3-kinase (PI3K) is a part is not an exception. In fact, dysregulated activation of PI3K signalling pathways can result in unbridled cellular proliferation and enhanced cell survival, thereby fostering the onset and advancement of cancer. Therefore, there is substantial interest in developing targeted therapies specifically aimed at inhibiting the PI3K enzyme and its associated pathways. Also, the therapeutic interest on pyrazoles and indazoles has been growing due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as PI3K inhibitors, and they showed promising results. There are already some PI3K inhibitors approved by Food and Drug Administration (FDA), such as Idelalisib (Zydelig®) and Alpelisib (Piqray®). In this context, this review aims to address the importance of PI3K in cellular processes and its role in cancer. Additionally, it aims to report a comprehensive literature review of PI3K inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PI3K inhibitors.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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