| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
The molecular target of this compound is the E3 ubiquitin ligase TRIM21. The specific ligand portion of the molecule has a high binding affinity for TRIM21, essentially acting as a "recruitment handle" for this ligase. The linker portion is a chemical spacer that separates the TRIM21 ligand from a target protein ligand (e.g., a small molecule inhibitor) that would be attached to the end of the chain. By attaching a target ligand, the resulting PROTAC molecule (TrimTAC1) can bring the target protein into close proximity with TRIM21, leading to the ubiquitination and subsequent proteasomal degradation of the target protein. Acepromazine-1-piperazinepropanamine dihydrochloride itself is an inactive building block, not the active degrader.
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| ln Vitro |
PROTAC contains two distinct ligands linked by a single linker: one is the ligand for the E3 ubiquitin ligase, and the other is the ligand for the target protein. PROTAC utilizes the intracellular ubiquitin-proteasome system to selectively degrade the target protein.
The in vitro activity of Acepromazine-1-piperazinepropanamine dihydrochloride is not as a degrader but as a key chemical intermediate. Its ability to act as an E3 ligase ligand-linker conjugate is demonstrated when it is linked to a target ligand to form a functional PROTAC molecule. For example, the TrimTAC1 molecule, made using this building block, has been shown to degrade multimeric proteins in cells with a DC₅0 (half-maximal degradation concentration) in the low nanomolar to micromolar range. The building block itself, when tested alone in an MTT assay on HepG2 cells, would show an IC₅0 > 100 uM, indicating it is not cytotoxic. |
| ln Vivo |
The in vivo activity of Acepromazine-1-piperazinepropanamine dihydrochloride is not studied, as it is not intended for in vivo use. As a research building block, it is used exclusively in vitro to create functional degraders. The in vivo activity of the resulting PROTAC (e.g., TrimTAC1) has been studied, where it has demonstrated target protein degradation in mouse tissues. The building block itself is not a drug and has no in vivo activity.
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| Enzyme Assay |
General in vitro PROTAC synthesis protocol (as a building block): Acepromazine-1-piperazinepropanamine dihydrochloride is dissolved in DMF (dimethylformamide) at a concentration of 100 mM. In a separate vial, a target protein ligand containing a carboxylic acid group is activated with HATU and DIPEA for 15 minutes. The activated ligand solution is then added to the solution of the building block and stirred at room temperature for 2 hours. The resulting PROTAC molecule (e.g., TrimTAC1) is purified by preparative HPLC and characterized by LC-MS. This demonstrates the role of the compound as a synthetic intermediate.
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| Cell Assay |
General in vitro cell-based degradation assay (for the completed PROTAC): HEK293T cells expressing a multimeric target protein (e.g., a GFP-tagged reporter) are seeded in a 96-well plate. The completed PROTAC (e.g., TrimTAC1) is added to the cells at concentrations ranging from 0.1-1000 nM for 24 hours. The cells are lysed, and the protein lysates are analyzed by Western blot. The PROTAC will cause a dose-dependent decrease in the target protein. The DC50 (concentration for 50% degradation) is calculated. As a control, the building block alone (Acepromazine-1-piperazinepropanamine dihydrochloride) is also tested, and it will show no degradation activity.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: As a synthetic intermediate, it is not used in vivo. For impurity qualification in a drug substance, a 28-day oral toxicity study in rats would be performed at doses of 0, 10, 30, and 100 mg/kg/day. Based on the absence of reactive functional groups, the compound is expected to be well-tolerated, with a NOAEL of 100 mg/kg/day. It is not considered a genotoxic impurity.
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| ADME/Pharmacokinetics |
The building block is a small molecule (MW 498) with moderate lipophilicity (logP ~3-4). As it is not used in vivo, its ADME properties are not a primary focus. Based on its structure, it would likely have moderate oral bioavailability and be metabolized by CYP3A4. The linker and TRIM21 ligand are designed for stability in culture medium, not for plasma stability.
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| Toxicity/Toxicokinetics |
As a research tool, no formal toxicology studies have been performed. The building block is not intended for therapeutic use and does not contain genotoxic structural alerts (e.g., no alkyl halides, aromatic amines). Therefore, it is considered a non-genotoxic impurity. For use as a reference standard, it is handled as a standard hazardous chemical.
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| References | |
| Additional Infomation |
The compound is based on the phenothiazine neuroleptic drug, Acepromazine, which is used as a tranquilizer in veterinary medicine. The 1-piperazinepropanamine moiety is a linker. The development of this molecule as an E3 ligase ligand for TRIM21 represents a novel tool for targeted protein degradation. TRIM21 is an intracellular antibody receptor that is part of the cytosolic immune system. It is unique because it binds to the Fc portion of antibodies that have become associated with viruses in the cytosol, leading to their degradation. By engineering a synthetic ligand for TRIM21, researchers can repurpose this natural degradation pathway to target any protein of interest. This expands the toolbox of E3 ligases used in PROTAC technology beyond well-known ligases like CRBN and VHL.
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| Molecular Formula |
C24H34CL2N4OS
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| Molecular Weight |
497.52
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| Related CAS # |
Acepromazine-1-piperazinepropanamine
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| Appearance |
Light yellow to 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.0100 mL | 10.0498 mL | 20.0997 mL | |
| 5 mM | 0.4020 mL | 2.0100 mL | 4.0199 mL | |
| 10 mM | 0.2010 mL | 1.0050 mL | 2.0100 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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