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| 10mg |
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| Targets |
Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3). SNIPER(TACC3)-2 is a TACC3 protein degrader. It is based on an IAP (Inhibitor of Apoptosis Protein) E3 ligand (Bestatin) conjugated to a TACC3-binding ligand via a linker. It recruits an E3 ubiquitin ligase (IAP) to TACC3, leading to its poly-ubiquitylation and proteasomal degradation. This activity induces cancer cell death.
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| ln Vitro |
In vitro, SNIPER(TACC3)-2 effectively and selectively degrades the TACC3 protein. The degradation of TACC3 leads to the suppression of cancer cell growth and the induction of cell death. Importantly, it has been shown to induce cell death selectively in cancer cells that express a larger amount of the TACC3 protein compared to normal cells, suggesting a potential therapeutic window.
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| ln Vivo |
In vivo, SNIPER(TACC3)-2 demonstrates that pharmacological degradation of TACC3 is a viable strategy. While detailed in vivo studies are part of ongoing research, the mechanism suggests that systemic administration could lead to tumor growth inhibition. It has been shown to sensitize cancer cells to other treatments, such as the proteasome inhibitor Bortezomib, suggesting potential for combination therapies.
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| Enzyme Assay |
A non-cell-based ubiquitination assay is used. Purified TACC3 protein and the IAP E3 ligase complex are mixed with SNIPER(TACC3)-2 (0-1000 nM) in ubiquitination buffer containing ATP, E1, and E2 enzymes. The reaction is incubated at 37degC for 60 min. The reaction is then analyzed by Western blotting with an anti-ubiquitin antibody to detect high-molecular-weight poly-ubiquitin chains.
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| Cell Assay |
Cancer cells (e.g., HeLa or other TACC3-high expressing cells) are seeded in 6-well plates. The next day, cells are treated with SNIPER(TACC3)-2 at concentrations ranging from 0.1 to 1000 nM for 6-24 hours. Cells are harvested, lysed, and analyzed by Western blotting using an anti-TACC3 antibody. The DC50 (half-maximal degradation concentration) is calculated by densitometry. Cell viability is assessed after 48-72 hours of treatment using an MTT assay.
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| Animal Protocol |
Xenograft mouse model: Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with cancer cells. Once tumors reach ~100 mm3, mice are randomized into groups (n=6-8). SNIPER(TACC3)-2 is administered via intraperitoneal injection at 10-50 mg/kg, daily or every other day for 14-21 days. Tumor volume is measured every 2-3 days. Tumors are collected and analyzed for TACC3 protein levels by Western blot and immunohistochemistry.
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| ADME/Pharmacokinetics |
SNIPER(TACC3)-2 is a research chemical with a molecular weight of 848.07. It is typically formulated in 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% ddH2O for intraperitoneal administration. PK studies are ongoing, but as a SNIPER compound, it is expected to have moderate bioavailability and a short to medium half-life, typical for small-molecule PROTACs. The compound is soluble in DMSO (100 mg/mL).
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| Toxicity/Toxicokinetics |
SNIPER(TACC3)-2 is for research use only and is not approved for human use. In preclinical studies, no acute toxicity has been reported at standard doses (e.g., 10-50 mg/kg i.p.). Because it induces cancer cell death, potential on-target toxicity might occur in normal proliferating tissues where TACC3 is expressed. Standard laboratory safety precautions should be used, as this is an active biological molecule.
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| References | |
| Additional Infomation |
SNIPER(TACC3)-2 is a research tool that has not entered clinical trials. It represents a powerful chemical biology approach to validate TACC3 as a drug target for cancer therapy. Unlike typical inhibitors, a degrader has the advantage of removing the entire protein, not just blocking its activity. The compound should be stored at -20degC as a powder, protected from moisture and light.
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| Molecular Formula |
C43H61N9O7S
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| Molecular Weight |
848.07
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| Related CAS # |
SNIPER(TACC3)-2 hydrochloride
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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 |
| 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 (~117.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.95 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 25.0 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: ≥ 2.5 mg/mL (2.95 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 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: ≥ 2.5 mg/mL (2.95 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 | 1.1791 mL | 5.8957 mL | 11.7915 mL | |
| 5 mM | 0.2358 mL | 1.1791 mL | 2.3583 mL | |
| 10 mM | 0.1179 mL | 0.5896 mL | 1.1791 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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