GNE-6640

GNE-6640 is a selective and non-covalent inhibitor of ubiquitin epecific peptidase 7 (USP7), with IC50 values of 0.75 μM, 0.43 μM, 20.3 μM and 0.23 μM for full length USP7, USP7 catalytic domain, full length USP43 and Ub-MDM2, respectively.

Signaling Pathways >> Cell Cycle/DNA Damage >> Deubiquitinase

Research Areas >> Cancer

IC50: 0.75 μM(full length USP7), 0.43 μM(USP7 catalytic domain), 20.3 μM(full length USP43), 0.23 μM(Ub-MDM2)[1].

GNE-6640 promotes endogenous MDM2 ubiquitination with Lys48 (K48)-linked polyubiquitin chains, which directs proteasomal degradation13. GNE-6640 targets cellular USP7, MDM2, and p53 signalling pathways. GNE-6640 decreases viability of 108 cell lines with IC50 ≤ 10 μM. Combining GNE-6640 with doxorubicin or cisplatin (DNA-damaging agents), which could activate the p53 response and enhance USP7 inhibitor efficacy. GNE-6640 could induce tumor cell death. GNE-6640 enhances cytotoxicity with chemotherapeutic agents and targeted compounds, including PIM kinase inhibitors[1].

[1]. Kategaya L, et al. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26;550(7677):534-538.

BAY 11-7082 | P5091 | PR-619 | VLX1570 | Degrasyn(WP1130) | P 22077 | DUBs-IN-2 | ML364 | NSC 687852 | GNE-6776 | ML 323 | HBX 19818 | IU1 | LDN-57444