| Targets |
CST967 targets ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme involved in the regulation of protein stability and cellular processes. USP7 is a therapeutic target in cancer due to its role in stabilizing oncoproteins and tumor suppressors. CST967 is a PROTAC that induces the degradation of USP7 by recruiting the CRBN E3 ubiquitin ligase. This leads to ubiquitination and proteasomal degradation of USP7, resulting in apoptosis in multiple cancer cell lines.
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| ln Vitro |
In vitro, CST967 has been shown to potently and selectively degrade USP7. Increasing the PROTAC concentration enhances the degradation rate of USP7. The compound exhibits a DC50 of 17 nM and a Dmax of 85% at 1 μM. CST967 inhibits the proliferation of USP7-dependent cancer cells. The compound's selectivity for USP7 over other deubiquitinating enzymes has been demonstrated. CST967 treatment leads to apoptosis in multiple cancer cell lines.
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| ln Vivo |
In vivo, CST967 has demonstrated antitumor efficacy in mouse models. The compound is the first reported deubiquitinase (DUB) degrader and serves as a useful tool to deepen understanding of USP7 biology. CST967 can be used in cancer research to study the role of USP7 in tumorigenesis and as a potential therapeutic strategy. The compound's in vivo efficacy has been evaluated in USP7-dependent cancer models.
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| Enzyme Assay |
In vitro assays for CST967 involve measuring USP7 degradation in cell-based systems. Cells are treated with CST967 at various concentrations, and USP7 protein levels are quantified by Western blotting or ELISA. DC50 values are calculated from dose-response curves. Dmax represents the maximum degradation achieved at saturating concentrations. Selectivity is assessed by profiling against other deubiquitinating enzymes using activity-based probes or immunoblotting. Cellular proliferation is measured using standard viability assays.
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| Cell Assay |
In vitro cellular assays for CST967 use cancer cell lines that are dependent on USP7 for proliferation. Cells are cultured in appropriate media and treated with CST967 at concentrations ranging from nanomolar to micromolar. USP7 degradation is assessed by Western blotting. Cell viability and proliferation are measured using MTT, CellTiter-Glo, or colony formation assays. Apoptosis is evaluated by measuring caspase activity, Annexin V staining, or PARP cleavage. The compound's effects on downstream signaling pathways are also assessed.
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| Animal Protocol |
In vivo animal studies for CST967 involve administration to tumor-bearing mouse models. The compound is typically administered by intraperitoneal or oral routes. Tumor growth is monitored by caliper measurement, and tumor tissues are collected for analysis of USP7 degradation and biomarker modulation. Pharmacodynamic studies assess the correlation between USP7 degradation and antitumor efficacy. The compound's effects on systemic immune homeostasis are also evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for CST967 are not fully detailed in the available literature. As a PROTAC, the compound has a higher molecular weight than typical small molecules, which may affect its oral bioavailability and tissue distribution. The compound's pharmacokinetic profile would include assessment of absorption, distribution, metabolism, and excretion. PROTACs generally have moderate to poor oral bioavailability and are often administered via intraperitoneal injection in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for CST967 are limited. As a research compound, comprehensive toxicological assessments have not been widely reported. The compound's selectivity for USP7 suggests that off-target effects may be limited. However, as a PROTAC that induces protein degradation, potential toxicities related to USP7 loss in normal tissues should be considered. USP7 has roles in various cellular processes, and its degradation may cause adverse effects. Further studies are needed to evaluate the safety profile.
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| References | |
| Additional Infomation |
CST967 is a research tool for studying USP7 biology and a potential therapeutic agent for cancer treatment. It is the first reported deubiquitinase (DUB) degrader and serves as a useful tool to deepen understanding of USP7. The compound causes highly selective degradation of USP7 and inhibits proliferation of USP7-dependent cancer cells. CST967 is a PROTAC (PROteolysis TArgeting Chimera) that recruits CRBN E3 ligase to ubiquitinate and degrade USP7. The compound is not approved for clinical use.
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| Molecular Formula |
C51H58N8O9
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|---|---|
| Molecular Weight |
927.05
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO :~100 mg/mL (~107.87 mM; with sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0787 mL | 5.3935 mL | 10.7869 mL | |
| 5 mM | 0.2157 mL | 1.0787 mL | 2.1574 mL | |
| 10 mM | 0.1079 mL | 0.5393 mL | 1.0787 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.
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