For research use only. Not for therapeutic Use.
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[1][2].
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].
| CAS Number | 2009273-67-8 |
| Synonyms | 4-[2-amino-4-ethyl-5-(1H-indazol-5-yl)pyridin-3-yl]phenol |
| Molecular Formula | C20H18N4O |
| Purity | ≥95% |
| InChI | InChI=1S/C20H18N4O/c1-2-16-17(13-5-8-18-14(9-13)10-23-24-18)11-22-20(21)19(16)12-3-6-15(25)7-4-12/h3-11,25H,2H2,1H3,(H2,21,22)(H,23,24) |
| InChIKey | ZHYXJQQBKROZDX-UHFFFAOYSA-N |
| SMILES | CCC1=C(C(=NC=C1C2=CC3=C(C=C2)NN=C3)N)C4=CC=C(C=C4)O |
| Reference | [1]. Kategaya L, et al. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26;550(7677):534-538. [2]. Tanguturi P, et al. The role of deubiquitinating enzymes in cancer drug resistance. Cancer Chemother Pharmacol. 2020 Apr;85(4):627-639. |
