Synonyms: compound 5 [PMID: 36442664]
Compound class:
Synthetic organic
Comment: This compound is a PROTAC that targets the NAD+ synthesising enzyme nicotinamide phosphoribosyltransferase (NAMPT) to the ubiquitin-proteasome system for degradation [1]. Its NAMPT-binding warhead (inhibitor M049-0244 [2]) is a fluorescent ligand that allows monitoring of degradation within cells, and it uses a VHL ligand to engage the E3 ligase. Reducing intracellular NAD+ levels is an approach that is exploited to inhibit the expansion of rapidly proliferating cancer cells.
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References |
1. Cheng J, He S, Xu J, Huang M, Dong G, Sheng C. (2022)
Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT. J Med Chem, 65 (23): 15725-15737. [PMID:36442664] |
2. Wang X, Xu TY, Liu XZ, Zhang SL, Wang P, Li ZY, Guan YF, Wang SN, Dong GQ, Zhuo S et al.. (2015)
Discovery of Novel Inhibitors and Fluorescent Probe Targeting NAMPT. Sci Rep, 5: 12657. [PMID:26227784] |