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Purity: ≥98%
GNE-6776 HCl (GNE6776), the hydrochloride salt of GNE-6776 which is an analog of GNE-6640, is a novel potent and selective inhibitor of USP7 (ubiquitin-specific protease-7) with potential anticancer activity. In combination with targeted compounds such as PIM kinase inhibitors, it increases cytotoxicity and causes tumor cell death. According to structural analyses, GNE-6776 targets USP7 12 Å away from the catalytic cysteine non-covalently. Inhibiting USP7 deubiquitinase activity, GNE-6776 reduces ubiquitin binding. USP7 appears to preferentially interact and cleave ubiquitin moieties that have free Lys48 side chains, as evidenced by its interactions with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain. Deubiquitinase enzymes break down ubiquitin from substrates and are linked to various diseases. For instance, USP7, a protease specific to ubiquitin, controls the stability of the p53 tumour suppressor and other proteins that are essential for the survival of tumour cells.
| Targets |
USP7 (IC50 = 1.4 μM)
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| ln Vitro |
USP7 or HAUSP (herpesvirus-associated USP) is a deubiquitylating enzyme that cleaves ubiquitin from its substrates. It is also known as a ubiquitin-specific protease. USP7 is a eubiquitinase (DUB) that modifies the stability of Mdm2, p53, PTEN, and FOXO4 in order to regulate cell proliferation[1].
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| ln Vivo |
GNE-131 exhibits poor clearance in mice, rats, and dogs when in vivo.
GNE-131 shows outstanding effectiveness in a transgenic mouse model of pain as well. |
| References |
| Molecular Formula |
C20H20N4O2-HCL
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| Molecular Weight |
348.406
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| Exact Mass |
348.16
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| Elemental Analysis |
C, 68.95; H, 5.79; N, 16.08; O, 9.18
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| CAS # |
2009273-60-1
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
O=C(C1=CC=C(C2=C(CC)C(C3=CC=C(O)C=C3)=C(N)N=C2)C=N1)NC
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| InChi Key |
UCYSSYGGXOFJKK-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
6'-Amino-4'-ethyl-5'-(4-hydroxyphenyl)-N-methyl-[3,3'-bipyridine]-6-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8702 mL | 14.3509 mL | 28.7018 mL | |
| 5 mM | 0.5740 mL | 2.8702 mL | 5.7404 mL | |
| 10 mM | 0.2870 mL | 1.4351 mL | 2.8702 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Identification and characterization of USP7 inhibitors.Nature.2017 Oct 26;550(7677):534-538. |
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 Selectivity of USP7 inhibitors and synergy with PIM kinase inhibition.
USP7 inhibitors compete with ubiquitin binding to USP7.Nature.2017 Oct 26;550(7677):534-538. |
 USP7 preferentially binds and cleaves ubiquitin moieties with free K48 side chains.Nature.2017 Oct 26;550(7677):534-538. |
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