An overview of RAF kinases and their inhibitors (2019-2023).

Autor: Hashem O; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates., Shahin AI; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates., Al Hindawi MA; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates., Fageeri MF; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates., Al-Sbbagh SA; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates., Tarazi H; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates., El-Gamal MI; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. Electronic address: drmelgamal2002@gmail.com.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2024 Sep 05; Vol. 275, pp. 116631. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1016/j.ejmech.2024.116631
Abstrakt: Protein kinases (PKs) including RAF, perform a principal role in regulating countless cellular events such as cell growth, differentiation, and angiogenesis. Overexpression and mutation of RAF kinases are significant contributors to the development and spread of cancer. Therefore, RAF kinase inhibitors show promising outcomes as anti-cancer small molecules by suppressing the expression of RAF protein, blocking RAS/RAF interaction, or inhibiting RAF enzymes. Currently, there are insufficient reports about approving drugs with minimal degree of toxicity. Therefore, it is an urgent need to develop new RAF kinase inhibitors correlated with increased anticancer activity and lower cytotoxicity. This review outlines reported RAF kinase inhibitors for cancer treatment in patents and literature from 2019 to 2023. It highlights the available inhibitors by shedding light on their chemical structures, biochemical profiles, and current status. Additionally, we highlighted the hinge region-binding moiety of the reported compounds by showing the hydrogen bond patterns of representative inhibitors with the hinge region for each class. In recent years, RAF kinase inhibitors have gained considerable attention in cancer research and drug development due to their potential to be studied under clinical trials and their demonstration of various degrees of efficacy and safety profiles across different cancer types. However, addressing challenges related to drug resistance and safety represents a major avenue for the optimization and enhancement of RAF kinase inhibitors. Strategies to overcome such obstacles were discussed such as developing novel pan-RAF inhibitors, RAF dimer inhibitors, and combination treatments.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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