详情描述
GNE-6776 is a potent, non-covalent, selective and orally bioavailable inhibitor of USP7 with IC50 of 1.34 μM and 0.61 μM for full length USP7 and USP7 catalytic domain, respectively.
Product information
CAS Number: 2009273-71-4
Molecular Weight: 348.40
Formula: C20H20N4O2
Chemical Name: 5-[6-amino-4-ethyl-5-(4-hydroxyphenyl)pyridin-3-yl]-N-methylpyridine-2-carboxamide
Smiles: CCC1=C(C(N)=NC=C1C1=CN=C(C=C1)C(=O)NC)C1C=CC(O)=CC=1
InChiKey: UCYSSYGGXOFJKK-UHFFFAOYSA-N
InChi: InChI=1S/C20H20N4O2/c1-3-15-16(13-6-9-17(23-10-13)20(26)22-2)11-24-19(21)18(15)12-4-7-14(25)8-5-12/h4-11,25H,3H2,1-2H3,(H2,21,24)(H,22,26)
Technical Data
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO 70 mg/mL (200.92 mM) Ethanol 2 mg/mL (5.74 mM)
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-6776 non-covalently targets USP7 12 Å distant from the catalytic cysteine. GNE-6776 attenuates ubiquitin binding and thus inhibits USP7 deubiquitinase activity. GNE-6776 interacts with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain. GNE-6776 targets cellular USP7, MDM2, and p53 signalling pathways.GNE-6776 selectively inhibits recombinant USP7 relative to 36 other deubiquitinases. GNE-6776 remains selective even at 100 μM, a more than sixfold higher concentration than used in cellular assays. GNE-6776 significantly inhibits USP7 while remaining selective against 44-47 other detected deubiquitinases.
In Vivo:
Although efficacious exposure is only transiently achieved, GNE-6776 causes modest, although significant, EOL-1 xenograft growth delay.
References:
- Lorna Kategaya, et al. Nature. 2017 Oct 26;550(7677):534-538.
Products are for research use only. Not for human use.