| Targets |
As a PROTAC linker, 1-Bromo-4-(4-bromobutyl)benzene does not have direct biological targets. Its role is to serve as a chemical building block for the synthesis of PROTAC molecules. The two bromine atoms can undergo nucleophilic substitution reactions with amines, thiols, or other nucleophiles, enabling the attachment of E3 ubiquitin ligase ligands and target protein ligands. The 4-carbon butyl chain provides a flexible spacer between the aromatic ring and the attachment points, while the benzene ring adds rigidity and hydrophobic character to the linker region of the resulting PROTAC.
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| ln Vitro |
PROTAC contains two distinct ligands linked by a single linker: one is the ligand for the E149 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.
This compound does not have direct in vitro biological activity as it is a chemical linker. In PROTAC development, the compound is first reacted with nucleophilic functional groups on target protein ligands and E3 ligase ligands. The resulting PROTAC is then evaluated in cellular assays for target protein degradation. The butyl chain length (4 carbons) is among the most common spacer lengths for PROTACs, and the aromatic ring can contribute to overall PROTAC stability and cellular permeability. |
| ln Vivo |
No direct in vivo activity has been reported for this compound alone. For PROTACs synthesized using this building block, in vivo efficacy is typically evaluated in xenograft mouse models. The PROTAC is administered via intraperitoneal or intravenous injection, and target protein degradation in tumor tissues is assessed by western blotting. The butyl chain provides flexibility that can facilitate ternary complex formation, while the aromatic ring can enhance membrane permeability and metabolic stability compared to purely aliphatic linkers.
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| Enzyme Assay |
No specific enzyme/receptor binding protocols have been established for this compound. Standard synthetic protocols for using 1-Bromo-4-(4-bromobutyl)benzene in PROTAC synthesis involve nucleophilic substitution reactions. Typically, one equivalent of the dibromo compound is reacted with an amine-containing E3 ligase ligand or target protein ligand in the presence of a base (e.g., K2CO3, NaH, or DIPEA) in an aprotic solvent such as DMF, DMSO, or THF at room temperature or elevated temperatures (40-80degC) for 12-24 hours. After purification, the remaining bromine is reacted with a second nucleophile to attach the other ligand. For cross-coupling approaches, the aromatic bromine can undergo Suzuki-Miyaura reactions with boronate esters. The product is purified by column chromatography or preparative HPLC.
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| Cell Assay |
1-Bromo-4-(4-bromobutyl)benzene is not evaluated in cellular assays directly. For cellular evaluation of PROTACs synthesized using this building block, standard protocols involve culturing cancer cell lines (e.g., HEK293, HeLa, MCF-7, or A549) in DMEM or RPMI-1640 with 10% FBS at 37degC in 5% CO2. Cells are seeded in 12- or 96-well plates at appropriate densities and allowed to attach overnight. PROTAC is added at concentrations ranging from 0.1 nM to 10 uM for 4-72 hours. Target protein degradation is assessed by western blotting of cell lysates using specific primary antibodies. Cell viability is measured using MTT or CellTiter-Glo assays. All conditions are tested in triplicate for statistical reliability.
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| Animal Protocol |
For in vivo studies using PROTACs synthesized with this building block, standard animal protocols involve xenograft models in immunodeficient mice (nude or NSG mice, 6-8 weeks old, 18-22 g). Approximately 5×10⁶ cancer cells in 100 uL PBS mixed 1:1 with Matrigel are injected subcutaneously into the flank. When tumors reach ~150-200 mm3, mice are randomized into treatment groups (n=5-10 per group). PROTAC is administered intraperitoneally or intravenously at doses of 1-50 mg/kg in formulation vehicles such as 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Tumor volumes (mm3 = length × width2 / 2) are measured every 2-3 days using digital calipers. Body weights are monitored as a toxicity indicator. At study termination, tumors are excised, weighed, and processed for target protein analysis by western blotting.
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| ADME/Pharmacokinetics |
No direct pharmacokinetic studies have been published for 1-Bromo-4-(4-bromobutyl)benzene. Computed properties include molecular formula C10H12Br2, molecular weight 292.01 g/mol. The compound has a predicted logP of approximately 3.5-4.0, indicating high lipophilicity due to the aromatic ring and two bromine atoms. For PROTACs synthesized using this building block, the butyl chain provides 4 carbon atoms of flexible spacing, while the aromatic ring contributes to overall molecular hydrophobicity and may enhance membrane permeability. The final pharmacokinetic properties are determined by the complete PROTAC structure.
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| Toxicity/Toxicokinetics |
Safety data for 1-Bromo-4-(4-bromobutyl)benzene indicates the compound is for research use only. Standard laboratory safety precautions should be followed: wear protective gloves, safety goggles, and a lab coat. Work in a well-ventilated fume hood to avoid inhalation of dust or vapors. Avoid contact with skin and eyes. The compound should be stored at -20degC, protected from light and moisture. Brominated compounds can be hazardous; treat with appropriate care. The compound is not for human therapeutic use.
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| Additional Infomation |
1-Bromo-4-(4-bromobutyl)benzene is a PROTAC linker featuring a symmetrical dibromo structure with a benzene ring and a butyl chain. This compound is also known as 1-(4-Bromobutyl)-4-bromobenzene. The two bromine atoms provide orthogonal or sequential conjugation handles for attaching E3 ubiquitin ligase ligands and target protein ligands via nucleophilic substitution reactions (e.g., with amines, thiols, or alkoxides). The butyl chain provides 4-carbon flexible spacing, which is within the optimal linker length range of 12 to over 20 total carbons for PROTAC activity. The aromatic ring adds rigidity and hydrophobic character, which can influence ternary complex formation and cellular permeability. This product is for research use only and has no approved clinical applications.
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| Exact Mass |
291.929
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|---|---|
| CAS # |
88999-91-1
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| PubChem CID |
57065284
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
12
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| Complexity |
106
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YWTSERISEGNNBO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H12Br2/c11-8-2-1-3-9-4-6-10(12)7-5-9/h4-7H,1-3,8H2
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| Chemical Name |
1-bromo-4-(4-bromobutyl)benzene
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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.) |
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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