Deubiquitinase Degrader

U7D-1 is a USP7 PROTAC degrader that induces selective proteasomal degradation of USP7. U7D-1 destabilizes and downregulates the expression of variant PRC1 complex subunits PCGF1, RING1A and PCGF6, and also slightly reduces the protein level of KDM2B. U7D-1 decreases cell viability, arrests neuroblastoma cells at the G0/G1 cell cycle phase, and downregulates the expression of target genes of PAX3::FOXO1 in FP-RMS cells. U7D-1 increases the level of cleaved PARP in FP-RMS cells, induces cell apoptosis, and upregulates the expression of muscle differentiation markers MYH1 and MYF5. U7D-1 inhibits the growth and proliferation of p53 wild-type and mutant cancer cells, and regulates the apoptosis pathway and E2F pathway. U7D-1 is applicable to studies on neuroblastoma, fusion-positive rhabdomyosarcoma, p53-mutant cancers and cancer-related research.

PROTAC USP39 Degrader-1 is a USP39 PROTAC degrader with K_d values of 136 nM and 232 nM, and a DC₅₀ value of 1.06 nM (24 h). PROTAC USP39 Degrader-1 binds to the VHL E3 ubiquitin ligase, forms a ternary complex with USP39, mediates USP39 ubiquitination and proteasomal degradation dependent on VHL recruitment, modulates splicing activity and induces 5' splice site-specific splicing patterns. PROTAC USP39 Degrader-1 can be used in the research of cervical cancer.

PROTAC USP7 Degrader-1 is a VHL-recruiting PROTAC and USP7 degrader with binding activity to both USP7 and the VHL E3 ubiquitin ligase. PROTAC USP7 Degrader-1 recruits the VHL E3 ligase to mediate the ubiquitination and subsequent proteolytic degradation of USP7.

PROTAC USP7 Degrader-2 (Compound D16) is an efficient and selective USP7 PROTAC degrader with a DC₅₀ of 1.91 μM (in TE-12 cells). PROTAC USP7 Degrader-2 inhibits the migration of upper gastrointestinal tract (UGI) cancer cells and shows relatively weak anti-proliferative activity. PROTAC USP7 Degrader-2 can be used in the research of metastatic upper gastrointestinal cancer.

XM-U-14 is a selective PROTAC USP7 Degrader (DC₅₀: 0.74 nM in inducing USP7 degradation in RS4;11 cell line). XM-U-14 upregulates the levels of p53 and p21. XM-U-14 also significantly inhibits acute lymphoblastic leukemia (ALL) cell growth (IC₅₀: 0.5 nM and 8.3 nM for RS4;11 cells and Reh cells respectively). XM-U-14 induces apoptosis and cycle arrest. XM-U-14 inhibits tumor growth. (Blue: VHL ligand (HY-159465), Black: linker (HY-W539783); Pink: USP7 inhibitor (HY-159464)).