Nampt degrader-2 is a fluorescent PROTAC, which efficiently degrades NAMPT with an IC50 of 41.9 nM. Nampt degrader-2 binds to NAMPT and VHL to form a ternary complex and subsequently induced NAMPT degradation via ubiquitin-proteasome system (UPS). Nampt degrader-2 leads to significant reduction of NAD+ and exerts potent antitumor activities.
Nampt degrader-2 (Compound B4; 30 nM; 24 h) is able to degrade NAMPT with a DC50 value of 8.4 nM. Nampt degrader-2 enables the visualization of degradation in A2780 cells[1].Nampt degrader-2 (Compound B4) shows the best antitumor activity in suppression of the proliferation in A2780 cells (IC50 = 12.1 nM)[1].
Nampt degrader-2 (Compound B4; 10-30 mg/kg; i.p; once a day; for 14 consecutive days) shows excellent antitumor effects in a dose-dependent manner. And Nampt degrader-2 significantly decreases the NAMPT levels in the tumors[1].
References:
[1]. Junfei Cheng, et al. Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT. J Med Chem. 2022 Dec 8;65(23):15725-15737.