Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors
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Acknowledgments
We acknowledge Forma’s high speed synthesis group for their synthetic contributions and the ADME group for generating the microsomal and solubility data, Shohini Ganguly and Rashida Garcia-Dancey for helping to generate the cellular data, Lakshmanan Manikandan, Saradhi Vijay, and Danilal C. Sharma for generating the in vivo PK and efficacy data, Agilent Technologies (Woburn, MA) for generating the Rapidfire LCMS data, and Professor Yigong Shi’s group (Tsinghua University, Beijing, China) for
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Drug discovery targeting nicotinamide phosphoribosyltransferase (NAMPT): Updated progress and perspectives
2024, Bioorganic and Medicinal ChemistryField-based 3D-QSAR studies on amide- and urea-containing NAMPT inhibitors
2023, Chemometrics and Intelligent Laboratory SystemsAn RNA-binding-protein, NONO governs energy metabolism by regulating NAMPT in lung cancer
2020, Biochemical and Biophysical Research CommunicationsIdentification of small-molecule urea derivatives as novel NAMPT inhibitors via pharmacophore-based virtual screening
2020, Bioorganic and Medicinal ChemistryCitation Excerpt :In order to minimize these problems and further improve the effect, we have implemented a strategy that combines ligand-based with structure-based pharmacophore methods and also with molecular docking.36,37 In order to construct the pharmacophore models, 27 amide, cyanoguanidine and urea derivatives reported as NAMPT inhibitor and publicly available x-ray coligand structures in complex with NAMPT (PDBs: 4M6P, 4LTS, 4JNM) were gathered from published data2,16–26 and three dataset consisting of 28 compounds (27 NAMPT inhibitors and a x-ray coligand) in each set were created. Compounds in each dataset were categorized into an active and inactive set based on a pIC50 value which has greater than 5.5 and less than 5.5, respectively, resulted in 19 active and 9 inactive compounds (Table S1 in Supplementary Material).
Identification of potent triazolylpyridine nicotinamide phosphoribosyltransferase (NAMPT) inhibitors bearing a 1,2,3-triazole tail group
2019, European Journal of Medicinal ChemistryApoptosis induced by NAD depletion is inhibited by KN-93 in a CaMKII-independent manner
2015, Experimental Cell ResearchCitation Excerpt :Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of Nam to nicotinamide mononucleotide, which is the rate-limiting step of the salvage pathway of mammalian NAD biosynthesis. Screening of anti-cancer agents using cell-based assays has identified several NAMPT inhibitors, a proportion of which are effective in animal models of cancer and autoimmune disease as well as in vitro assays [2–5]. NAMPT inhibitors deplete NAD via inhibition of the salvage pathway from Nam, which is followed by reduction of mitochondrial membrane potential and apoptosis [2,6].