U7D-1 is a first-in-class potent and selective USP7 (ubiquitin-specific protease 7) PROTAC degrader, with a DC50 of 33 nM in RS4;11 cells. U7D-1 shows anticancer activity. U7D-1 induces apoptosis in Jeko-1 cells.
U7D-1 (0-1 μM, 0-24 h) induced USP7 degradation in RS4;11 cell, reducing the USP7 protein level by 83.2% at 1 μM[1].U7D-1 (0-20 μM, 3 days) shows anti-proliferative activity in p53 wild-type cell lines, and maintains potent cell growth inhibition in p53 mutant cancer cells[1].U7D-1 (1 μM, 0-24 h) upregulates the level of p53 and p21 proteins in a time-dependent manner, and induces cleavage of caspase-3 in the Jeko-1 cell line in a time dependent manner[1]. U7D-1 (1 μM, 24 h) up-regulates the expression of apoptotic related genes and down-regulates the expression of E2F related genes in Jeko-1 cells[1].
References:
[1]. Pei Y, et al. Discovery of a Potent and Selective Degrader for USP7. Angew Chem Int Ed Engl. 2022 Aug 15;61(33):e202204395.