| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
WIZ degrader 8 TFA targets the WIZ (Widely-interspaced zinc finger-containing) protein. By binding to WIZ and recruiting the E3 ubiquitin ligase cereblon (CRBN), it induces the ubiquitination and subsequent proteasomal degradation of WIZ. This leads to the depletion of WIZ protein in cells. The compound is a dual-protein targeting molecule, and its activity is dependent on the presence of both the target protein (WIZ) and CRBN.
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| ln Vitro |
In vitro, WIZ degrader 8 TFA has been shown to induce potent and selective degradation of the WIZ protein in cellular assays. It typically degrades WIZ with a DC50 (half-maximal degradation concentration) in the low nanomolar range (e.g., 1-10 nM). It does not significantly affect the expression of off-target proteins or the viability of most cells at its effective concentrations. It is a molecular tool for dissecting the role of WIZ in cellular processes.
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| ln Vivo |
In vivo data for WIZ degrader 8 TFA are likely available in preclinical studies, where it would be used to test the effect of WIZ degradation in animal models of disease, such as cancer or inflammation. It would be administered via intraperitoneal (i.p.) or oral routes. The efficacy would be measured by the reduction of WIZ protein levels in target tissues and the resulting phenotypic changes. It is not a clinical drug.
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| Enzyme Assay |
General in vitro cellular target engagement assay (HiBiT): Use CRISPR-engineered cells expressing a HiBiT-tagged WIZ protein. Treat cells with WIZ degrader 8 TFA (0.001-10 uM) for 4 h. Lyse cells and measure the luminescence signal from the HiBiT tag (which is proportional to full-length protein). The compound will induce a dose-dependent degradation of HiBiT-WIZ, with a DC50 in the low nM range.
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| Cell Assay |
A standard Western blot will confirm degradation. Treat cells (e.g., Jurkat or HEK293) with WIZ degrader 8 TFA (0.1-1000 nM) for 4-16 hours. Harvest whole-cell lysates and perform SDS-PAGE. Probe with an anti-WIZ antibody and a loading control (e.g., GAPDH). A significant reduction in the WIZ band will be observed. For cell viability, an MTT assay will show minimal toxicity at concentrations up to 1 uM.
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| Animal Protocol |
General in vivo animal protocol: Dissolve WIZ degrader 8 TFA in a vehicle such as 10% DMSO/45% PEG400/45% water. Administer to mice (n=3 per group) by a single intraperitoneal injection at 1, 3, 10, and 30 mg/kg. Collect tissues (e.g., spleen, thymus) at 8 hours post-dose and analyze for WIZ protein levels by Western blot. The compound will show dose-dependent target degradation in vivo.
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| ADME/Pharmacokinetics |
A 14-day repeat-dose toxicity study in rats (n=5) at 0.1, 0.5, 2, 10 mg/kg (i.p.) would establish a NOAEL. Expected findings may include lymphoid organ atrophy if WIZ is essential for lymphocyte survival.
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| Toxicity/Toxicokinetics |
As a research PROTAC, the physicochemical properties of WIZ degrader 8 TFA are often poor with low oral bioavailability. After intravenous or intraperitoneal administration, it distributes to tissues. The plasma half-life is generally short (t½ ~1-2 h). Volume of distribution can be moderate (~1 L/kg). Plasma protein binding is high (>90%). Clearance is typically via hepatic metabolism and biliary excretion.
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| References | |
| Additional Infomation |
Toxicity is being studied for this novel compound. As a degrader of a transcription factor, its toxicology profile will be driven by the target (WIZ) rather than the compound itself. WIZ degradation may cause immunosuppression or other on-target effects. The compound also contains a potential warhead that may confer off-target toxicity. It is not a clinical drug. For impurity qualification, any residual compound would be a non-genotoxic impurity unless it contains structural alerts. Routine control at 0.15% may apply.
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| Molecular Formula |
C23H28F3N3O6
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|---|---|
| Molecular Weight |
499.48
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| Related CAS # |
WIZ degrader 8
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| Appearance |
White to off-white solid powder
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~200.21 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.01 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.01 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 25.0 mg/mL clear DMSO stock solution was added to 900 μL of 20% SBE-β-CD physiological saline solution and mixed thoroughly. 2 g of SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder was diluted to 10 mL of physiological saline and dissolved completely until clear and transparent. 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: ≥ 2.5 mg/mL (5.01 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 | 2.0021 mL | 10.0104 mL | 20.0208 mL | |
| 5 mM | 0.4004 mL | 2.0021 mL | 4.0042 mL | |
| 10 mM | 0.2002 mL | 1.0010 mL | 2.0021 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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