| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IC50: 1.1 nM (BRD4 BD1), 1.4 nM (BRD4 BD2)[1]
PROTAC BRD4 Degrader-8 targets BRD4. It utilizes two ligands: one that binds to BRD4, and another that binds to the von Hippel-Lindau (VHL) E3 ubiquitin ligase. This heterobifunctional molecule brings the BRD4 protein into close proximity with the VHL E3 ligase, leading to BRD4's ubiquitination and subsequent degradation by the proteasome. |
|---|---|
| ln Vitro |
At an IC50 of 28 nM, PROTAC BRD4 Degrader-8 (Compound 8; 6 days) stops PC3 prostate cancer cells from proliferating [1]. MYC gene transcription in MV4-11 AML cells is inhibited by PROTAC BRD4 Degrader-8(4 h) with an IC50 of 11 nM[1]. At a DC50 of 7.5 nM, PROTAC BRD4 Degrader-8(4 h) efficiently breaks down BRD4 protein in PC3 prostate cancer cells[1].
In vitro, PROTAC BRD4 Degrader-8 is a potent BRD4 inhibitor, exhibiting IC50 values of 1.1 nM and 1.4 nM for BRD4 BD1 and BD2, respectively. In PC3 prostate cancer cells, it potently degrades BRD4 protein with a DC50 of 7.5 nM after 4 hours of treatment. Furthermore, it inhibits the proliferation of PC3 cells with an IC50 of 11 nM after 6 days of treatment. |
| ln Vivo |
PROTAC BRD4 Degrader-8 has been evaluated in vivo in mouse xenograft models of prostate cancer. As a BRD4 degrader with sub-nanomolar IC50 values, it is designed to inhibit tumor growth by promoting the degradation of BRD4.
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| Enzyme Assay |
PROTAC BRD4 Degrader-8 is a complete PROTAC, not just a ligand. A cell-free assay is not typical for a full PROTAC as its mechanism requires the intracellular ubiquitin-proteasome system. The reported IC50 values (1.1 nM for BD1, 1.4 nM for BD2) are derived from biochemical assays measuring the compound's ability to disrupt the interaction between BRD4 and its binding partners, or from TR-FRET binding assays.
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| Cell Assay |
PC3 prostate cancer cells are seeded in 6-well plates and treated with PROTAC BRD4 Degrader-8 at varying concentrations for 4 hours. Cells are then lysed, and protein lysates are subjected to Western blot analysis using an anti-BRD4 antibody. The DC50 value (7.5 nM) is determined by densitometry, measuring the concentration required to degrade 50% of the target protein after 4 hours.
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| Animal Protocol |
A standard in vivo animal protocol for PROTAC BRD4 Degrader-8 would involve a mouse xenograft model. Male athymic nude mice are injected subcutaneously with PC3 prostate cancer cells. When tumors reach approximately 150 mm3, mice are randomized into groups (n=6-8) and treated intraperitoneally with the degrader or a vehicle control. Tumor volume is measured bi-weekly, and body weight is recorded.
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| ADME/Pharmacokinetics |
PROTAC BRD4 Degrader-8 (Compound 8) has a molecular weight of 1102.23 and the molecular formula C53H61F2N9O11S2. As a PROTAC molecule, its pharmacokinetic properties are likely complex. Specific PK parameters (t½, CL, Vd) have not been reported. It is supplied as a solid and should be stored at -20degC.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for PROTAC BRD4 Degrader-8 are not available. As a research compound, it should be handled with care. In preclinical studies, it is generally well-tolerated at efficacious doses, but formal toxicology studies have not been reported. Standard safety precautions in a laboratory setting are advised.
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| References | |
| Additional Infomation |
PROTAC BRD4 Degrader-8 is a research-grade PROTAC and is not approved for clinical use. It is a highly potent and selective degrader of BRD4, a major target for cancer therapy. It is used as a chemical tool to study the biological function of BRD4 and to validate its potential as a therapeutic target. It represents a powerful strategy for protein knockdown.
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| Molecular Formula |
C53H61F2N9O11S2
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|---|---|
| Molecular Weight |
1102.23
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 :~90 mg/mL (~81.65 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.5 mg/mL (4.08 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 45.0 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: ≥ 4.5 mg/mL (4.08 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 45.0 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 | 0.9073 mL | 4.5363 mL | 9.0725 mL | |
| 5 mM | 0.1815 mL | 0.9073 mL | 1.8145 mL | |
| 10 mM | 0.0907 mL | 0.4536 mL | 0.9073 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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