Nampt-KO Mouse

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is a key regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool. NAD is an essential coenzyme in cellular redox reactions and a substrate for NAD-dependent enzymes. NAMPT catalyzes the rate-limiting step in NAD biosynthesis from nicotinamide, influencing the activity of NAD-dependent enzymes and regulating cellular metabolism. It is involved in multiple biological processes and is associated with various metabolic and age-related disorders [1,3,4,7].

In cancer, NAMPT over-expression is a common strategy for tumors to sustain NAD production. Inhibiting NAMPT can deplete NAD and impair cellular metabolism in cancer cells. For example, in ovarian cancer, NAMPT inhibition suppresses cancer stem-like cells associated with therapy-induced senescence, and a combination of NAMPT inhibitor FK866 and cisplatin improves the survival of EOC-bearing mice [2]. In non-small cell lung cancer, lncRNA ITGB2-AS1 promotes cisplatin resistance by activating the FOSL2/NAMPT axis [5]. In necrotizing enterocolitis, NAMPT inhibitor FK866 relieves intestinal inflammation by regulating macrophage activation [6].

In conclusion, NAMPT is crucial for maintaining NAD levels and regulating cellular metabolism. Model-based research, especially through NAMPT inhibition in in vivo studies, has revealed its significant roles in cancer, intestinal inflammation, and other disease conditions. Understanding NAMPT's functions provides potential therapeutic strategies for these diseases [2,5,6,7].

References:

1. Garten, Antje, Schuster, Susanne, Penke, Melanie, de Giorgis, Tommaso, Kiess, Wieland. 2015. Physiological and pathophysiological roles of NAMPT and NAD metabolism. In Nature reviews. Endocrinology, 11, 535-46. doi:10.1038/nrendo.2015.117. https://pubmed.ncbi.nlm.nih.gov/26215259/

2. Nacarelli, Timothy, Fukumoto, Takeshi, Zundell, Joseph A, Borowsky, Mark E, Zhang, Rugang. 2019. NAMPT Inhibition Suppresses Cancer Stem-like Cells Associated with Therapy-Induced Senescence in Ovarian Cancer. In Cancer research, 80, 890-900. doi:10.1158/0008-5472.CAN-19-2830. https://pubmed.ncbi.nlm.nih.gov/31857293/

3. Velma, Ganga Reddy, Krider, Isabella S, Alves, Erick T M, Laham, Megan S, Thatcher, Gregory R J. 2024. Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death. In Journal of medicinal chemistry, 67, 5999-6026. doi:10.1021/acs.jmedchem.3c02112. https://pubmed.ncbi.nlm.nih.gov/38580317/

4. Ozgencil, Fikriye, Gunindi, Habibe Beyza, Eren, Gokcen. 2024. Dual-targeted NAMPT inhibitors as a progressive strategy for cancer therapy. In Bioorganic chemistry, 149, 107509. doi:10.1016/j.bioorg.2024.107509. https://pubmed.ncbi.nlm.nih.gov/38824699/

5. Chen, Huiyong, Wang, Linhui, Liu, Jingting, Liao, Hongliang, Wan, Renping. . LncRNA ITGB2-AS1 promotes cisplatin resistance of non-small cell lung cancer by inhibiting ferroptosis via activating the FOSL2/NAMPT axis. In Cancer biology & therapy, 24, 2223377. doi:10.1080/15384047.2023.2223377. https://pubmed.ncbi.nlm.nih.gov/37370246/

6. Liu, Qianyang, Gao, Kai, Ding, Xionghui, Chen, Gongli, Guo, Chunbao. 2023. NAMPT inhibition relieves intestinal inflammation by regulating macrophage activation in experimental necrotizing enterocolitis. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 165, 115012. doi:10.1016/j.biopha.2023.115012. https://pubmed.ncbi.nlm.nih.gov/37329710/

7. Gasparrini, Massimiliano, Giovannuzzi, Simone, Nocentini, Alessio, Raffaelli, Nadia, Supuran, Claudiu T. 2024. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) in cancer: a patent review. In Expert opinion on therapeutic patents, 34, 565-582. doi:10.1080/13543776.2024.2367006. https://pubmed.ncbi.nlm.nih.gov/38861278/