DA-PROTAC

DA-PROTAC is a potent PROTAC degrader of copper ion-transport proteins Atox1 and CCS. DA-PROTAC can bind both Atox1 and CCS proteins, and the complex can be bound to E3 ligase, leading to increased levels of ubiquitination of Atox1 and CCS and degradation of Atox1 and CCS proteins via the proteasome pathway. DA-PROTAC can be used for triple negative breast cancer research[1].

Research Areas >> Cancer

Signaling Pathways >> PROTAC >> PROTAC

Signaling Pathways >> PROTAC >> Ligand for E3 Ligase

VHL

DA-PROTAC (0-1 μM, 24 h) can degrade Atox1 and CCS proteins rather than inhibit Atox1 and CCS activity[1]. DA-PROTAC (5 μM, 24 h) inhibits the proliferation, migration and invasion of triple negative breast cancer cells (MDA-MB-231)[1]. DA-PROTAC (10 μM, 48 h) inhibits the tumorigenic capacity of triple negative breast cancer cells (MDA-MB-231)[1]. The targeting module of DA-PROTAC is a small molecule VHL ligand1 combined with E3 ligase[1]. Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 100 nM ,200 nM ,500 nM , and 1000 nM Incubation Time: 24 h Result: Significantly reduced ATOX1 and CCS protein levels under 200nM, indicating that DA-PROTAC can degrade ATOX1 and CCS proteins.

[1]. Zhao Yicheng, et al. Small-molecule inhibitor for degrading copper ion transporter Atox1 and CCS and application thereof. CN111471054A.