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.

Product information

CAS Number: 2009273-67-8

Molecular Weight: 330.38

Formula: C20H18N4O

Chemical Name: 4-[2-amino-4-ethyl-5-(1H-indazol-5-yl)pyridin-3-yl]phenol

Smiles: CCC1=C(C(N)=NC=C1C1=CC2C=NNC=2C=C1)C1C=CC(O)=CC=1

InChiKey: ZHYXJQQBKROZDX-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 5 mg/mL (15.13 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

References:

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

Products are for research use only. Not for human use.