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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Bioactivity Comments |
PROTAC B4's DC50 for degradation of human NAMPT is 8.4 nM [1]. It inhibits NAMPT enzymatic activity with an IC50 of 41.9 nM, and inhibits proliferation of A2780 human ovarian carcinoma cells with an IC50 of 12.1 nM. |