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| Targets |
Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3). SNIPER(TACC3)-1 hydrochloride is a degrader that targets TACC3 via the ubiquitin-proteasome system. It consists of a TACC3-binding ligand attached via a linker to a ligand for the IAP (Inhibitor of Apoptosis Protein) family of E3 ubiquitin ligases. This promotes the selective degradation of the TACC3 protein and induces cancer cell death.
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| ln Vitro |
In vitro, SNIPER(TACC3)-1 hydrochloride (0.1-1000 nM) induces the poly-ubiquitylation and proteasomal degradation of the TACC3 protein in HeLa cells. This degradation is selective, as the compound induces cancer cell death in cells with high TACC3 expression. It has been shown to sensitize cancer cells to the proteasome inhibitor Bortezomib. It reduces TACC3 protein levels in a concentration-dependent manner.
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| ln Vivo |
In vivo efficacy data for SNIPER(TACC3)-1 hydrochloride is limited. The key in vivo demonstration was that TACC3 protein could be degraded in a xenograft model. It is expected to have anti-proliferative effects. However, its development was succeeded by second-generation compounds. Research using this tool highlights the importance of TACC3 degradation in suppressing tumor growth and its potential in combination therapies.
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| Enzyme Assay |
A non-cell-based ubiquitination assay is performed. Recombinant TACC3 protein and the purified IAP E3 ligase complex are incubated with SNIPER(TACC3)-1 hydrochloride (0-1000 nM) in an assay buffer containing ATP, E1 activating enzyme, and E2 conjugating enzyme. The reaction is carried out at 37degC for 1 hour. Ubiquitinated TACC3 is detected by Western blot using an anti-ubiquitin antibody.
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| Cell Assay |
HeLa cells are seeded in 6-well plates. After 24 h, cells are treated with SNIPER(TACC3)-1 hydrochloride (0, 0.1, 1, 10, 100, 1000 nM). After 6-12 h of treatment, cells are lysed and protein is extracted. TACC3 protein levels are assessed by Western blotting using a specific anti-TACC3 antibody and quantified relative to a loading control (e.g., beta-actin) using densitometry.
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| Animal Protocol |
Xenograft model: Nude mice bearing human tumor xenografts are treated with SNIPER(TACC3)-1 hydrochloride via intraperitoneal injection at doses of 10-40 mg/kg, administered on a daily or bi-daily schedule for 2-3 weeks. Tumor growth and body weight are monitored. At study termination, tumors are excised and analyzed by Western blot for TACC3 protein levels to confirm target degradation.
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| ADME/Pharmacokinetics |
SNIPER(TACC3)-1 hydrochloride is a research compound with a molecular weight of 840.47 (MW for HCl salt). It is soluble in DMSO. The hydrochloride salt form enhances solubility and stability. For in vivo formulation, it can be dissolved in a vehicle containing DMSO, PEG300, Tween-80, and saline. Detailed PK parameters such as half-life and bioavailability are not readily available for this early-generation compound.
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| Toxicity/Toxicokinetics |
As a research compound, detailed toxicology data is not available. SNIPER(TACC3)-1 hydrochloride is for research use only and is not intended for diagnostic or therapeutic use in humans. It is a biologically active molecule that can induce cell death. Standard precautions for handling cytotoxic compounds should be observed, including the use of gloves and safety glasses in a well-ventilated area.
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| References | |
| Additional Infomation |
SNIPER(TACC3)-1 hydrochloride is one of the first SNIPER molecules reported. It is a research tool that served as a proof-of-concept for using IAP-based SNIPERs to target and degrade non-IAP proteins like TACC3. This compound is not a drug and has not been approved. It is available for research purposes to study protein degradation mechanisms. Store at -20degC as a powder.
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| Molecular Formula |
C41H57N9O6S
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| Molecular Weight |
804.01
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| Related CAS # |
SNIPER(TACC3)-1 hydrochloride
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| Appearance |
Off-white to light yellow 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 (~124.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.11 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 (3.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2438 mL | 6.2188 mL | 12.4377 mL | |
| 5 mM | 0.2488 mL | 1.2438 mL | 2.4875 mL | |
| 10 mM | 0.1244 mL | 0.6219 mL | 1.2438 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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