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HBX 41108

Catalog No.GC12622

Ubiquitin-specific protease (USP) 7 inhibitor

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HBX 41108 Chemical Structure

Cas No.: 924296-39-9

Size Price Stock Qty
1mg
$28.00
In stock
5mg
$126.00
In stock
10mg
$207.00
In stock
25mg
$486.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1, 2]:

Cell lines

HCT116 colon cancer cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

24 h

Applications

In HCT116 colon cancer cells, treated with various doses of HBX 41,108 (1, 3, and 10 μmol/L) for 24 h increased p53 levels in a nongenotoxic manner. HBX 41,108 inhibited USP7 activity in HEK293 cells transfected with USP7. HBX 41,108 (0.1-10 μM, 24 h) inhibited HCT116 cancer cell growth and induced apoptotic cell death. HBX 41,108 induced p53-dependent apoptosis in p53 wild-type and null isogenic cancer cell lines. In COS7 cells, HBX 41108 inhibited PPARγ stability induced by USP7 and decreased the basal transcriptional activity of PPARγ by 70%。

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Colland F, Formstecher E, Jacq X, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther, 2009, 8(8): 2286-2295.

[2]. Lee KW, Cho JG, Kim CM, et al. Herpesvirus-associated Ubiquitin-specific Protease (HAUSP) Modulates Peroxisome Proliferator-activated Receptor γ (PPARγ) Stability through Its Deubiquitinating Activity. J Biol Chem, 2013, 288(46): 32886-32896.

Background

HBX 41108 is a potent inhibitor of USP7 with IC50 value of 424 nM [1].

Ubiquitin-specific-processing protease 7 (USP7) is a ubiquitin specific protease and removes ubiquitin from specific protein substrates. USP7 can deubiquitinate p53, protecting p53 from Mdm2-mediated degradation and involving the oncogenic stabilization of p53.

HBX 41108 is an uncompetitive and reversible USP7 inhibitor. HBX 41108 inhibited USP7-mediated p53 deubiquitination with IC50 value of 0.8 μM in a dose-dependent way and was only weakly active against the aspartic, serine and metalloproteases tested with IC50 > 10 μM. In HCT116 cells, HBX 41108 increased the levels of p53 and p21cip1/waf, which was the product of p53 target genes. In HEK293 cells, HBX 41108 increased the level of polyubiquitinated forms of p53 and reduced Mdm2 levels. In HCT116 colon cancer cells, HBX 41108 inhibited cell proliferation with IC50 value of 1 μM in a dose-dependent way and induced apoptosis in a dose-dependent manner [1]. In COS7 cells, HBX 41108 inhibited PPARγ stability induced by USP7 and decreased the basal transcriptional activity of PPARγ by 70% [2].

References:
[1].  Colland F, Formstecher E, Jacq X, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther, 2009, 8(8): 2286-2295.
[2].  Lee KW, Cho JG, Kim CM, et al. Herpesvirus-associated Ubiquitin-specific Protease (HAUSP) Modulates Peroxisome Proliferator-activated Receptor γ (PPARγ) Stability through Its Deubiquitinating Activity. J Biol Chem, 2013, 288(46): 32886-32896.

Chemical Properties

Cas No. 924296-39-9 SDF
Chemical Name 7-chloro-9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile
Canonical SMILES ClC1=CC=C(C2=NC(C#N)=C(C#N)N=C2C3=O)C3=C1
Formula C13H3ClN4O M.Wt 266.64
Solubility 33mg/mL in DMSO; 25mg/mL in DMF; Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 3.7504 mL 18.7519 mL 37.5038 mL
5 mM 0.7501 mL 3.7504 mL 7.5008 mL
10 mM 0.375 mL 1.8752 mL 3.7504 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 1 reference(s) in Google Scholar.)

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