Novel PROTACs for degradation of SHP2 protein
M Zheng, Y Liu, C Wu, K Yang, Q Wang, Y Zhou… - Bioorganic …, 2021 - Elsevier
Protein tyrosine phosphatase SHP2 is a member of PTPs family associated with cancer such
as leukemia, non-small cell lung cancer, breast cancer, and so on. SHP2 is a promising
target for drug development, and consequently it is of great significance to develop SHP2
inhibitors. Herein, we report CRBN-recruiting PROTAC molecules targeting SHP2 by
connecting pomalidomide with SHP099, an allosteric inhibitor of SHP2. Among them, SP4
significantly inhibited the growth of Hela cells, compared with SHP099, its activity increased …
as leukemia, non-small cell lung cancer, breast cancer, and so on. SHP2 is a promising
target for drug development, and consequently it is of great significance to develop SHP2
inhibitors. Herein, we report CRBN-recruiting PROTAC molecules targeting SHP2 by
connecting pomalidomide with SHP099, an allosteric inhibitor of SHP2. Among them, SP4
significantly inhibited the growth of Hela cells, compared with SHP099, its activity increased …
Abstract
Protein tyrosine phosphatase SHP2 is a member of PTPs family associated with cancer such as leukemia, non-small cell lung cancer, breast cancer, and so on. SHP2 is a promising target for drug development, and consequently it is of great significance to develop SHP2 inhibitors. Herein, we report CRBN-recruiting PROTAC molecules targeting SHP2 by connecting pomalidomide with SHP099, an allosteric inhibitor of SHP2. Among them, SP4 significantly inhibited the growth of Hela cells, compared with SHP099, its activity increased 100 times. In addition, it can significantly induce SHP2 degradation and cell apoptosis. Further study of SHP2-protac may have important significance for the treatment of SHP2 related diseases.
Elsevier