Dual-targeted NAMPT inhibitors as a progressive strategy for cancer therapy.

Autor: Ozgencil F; SIRTeam Group, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Türkiye., Gunindi HB; SIRTeam Group, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Türkiye., Eren G; SIRTeam Group, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Türkiye. Electronic address: gokcene@gazi.edu.tr.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Aug; Vol. 149, pp. 107509. Date of Electronic Publication: 2024 May 29.
DOI: 10.1016/j.bioorg.2024.107509
Abstrakt: In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is a crucial enzyme in the nicotinamide adenine dinucleotide (NAD + ) synthesis pathway catalyzing the condensation of nicotinamide (NAM) with 5-phosphoribosyl-1-pyrophosphate (PRPP) to produce nicotinamide mononucleotide (NMN). Given the pivotal role of NAD + in a range of cellular functions, including DNA synthesis, redox reactions, cytokine generation, metabolism, and aging, NAMPT has become a promising target for many diseases, notably cancer. Therefore, various NAMPT inhibitors have been reported and classified as first and second-generation based on their chemical structures and design strategies, dual-targeted being one. However, most NAMPT inhibitors suffer from several limitations, such as dose-dependent toxicity and poor pharmacokinetic properties. Consequently, there is no clinically approved NAMPT inhibitor. Hence, research on discovering more effective and less toxic dual-targeted NAMPT inhibitors with desirable pharmacokinetic properties has drawn attention recently. This review summarizes the previously reported dual-targeted NAMPT inhibitors, focusing on their design strategies and advantages over the single-targeted therapies.
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 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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