| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Bromodomain-containing protein 4 (BRD4), an epigenetic reader protein involved in transcriptional regulation and cancer progression.
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|---|---|
| ln Vitro |
In PC3 prostate cancer cells, PROTAC BRD4 Degrader-10 achieves potent BRD4 protein degradation with DC50 (half-maximal degradation concentration) values of 1.3 nM when conjugated with a STEAP1 antibody and 18 nM when conjugated with a CLL1 antibody. These values demonstrate its high efficacy as a targeted protein degrader in a cellular context.
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| ln Vivo |
Relevant in vivo data for PROTAC BRD4 Degrader-10 as a standalone agent is not specified in the provided literature. However, its efficacy is established in cell-based assays, and it is designed for further investigation in animal models to evaluate its anti-tumor effects and pharmacokinetic properties.
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| Enzyme Assay |
Specific protocols for non-cellular enzyme/receptor binding assays for this specific degrader are not detailed in the search results. Generally, such assays for PROTACs involve a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay to measure ternary complex formation between BRD4, the PROTAC, and the VHL E3 ligase, or an AlphaScreen assay to assess binding affinity to the target protein BRD4.
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| Cell Assay |
The described in vitro degradation activity was assessed in PC3 prostate cancer cells. A typical protocol involves treating PC3 cells with varying concentrations of the PROTAC compound or its antibody conjugates. After a period of incubation (e.g., 24-48 hours), cells are lysed. The remaining BRD4 protein levels in the lysates are then quantified by standard Western blotting, which is used to determine the DC50 (the concentration needed to degrade 50% of the target protein).
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| Animal Protocol |
Specific in vivo experimental protocols for this compound are not available in the provided data. Animal studies would typically involve administering the compound or its antibody conjugates (e.g., STEAP1-conjugated) to tumor-bearing mouse models (e.g., PC3 xenografts). The primary endpoint is often tumor volume measurement, along with the analysis of BRD4 protein levels in harvested tumor tissues to confirm target engagement and pharmacodynamic effects.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is available in the provided information. As a PROTAC, its PK properties (such as oral bioavailability, half-life, and clearance) are generally a critical area of investigation in preclinical development to determine its suitability for in vivo use.
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| Toxicity/Toxicokinetics |
No specific toxicity information is provided in the search results. Toxicity profiling is a standard part of preclinical drug development and would be conducted in animal models to evaluate potential adverse effects at therapeutic and supratherapeutic doses.
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| References |
[1]. Dragovich PS, et, al. Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy. J Med Chem. 2021 Mar 11;64(5):2576-2607.
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| Additional Infomation |
PROTACs represent a novel pharmacological modality that degrades, rather than merely inhibits, a target protein. By working through a catalytic mechanism, they can offer advantages in overcoming drug resistance. This compound is a research tool for cancer biology and is not currently approved for clinical use. The provided chemical structure identifies it as a complex VHL-based PROTAC.
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| Molecular Formula |
C59H71F2N9O15S4
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|---|---|
| Molecular Weight |
1312.50315690041
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| Exact Mass |
1311.392
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| CAS # |
2417370-49-9
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| PubChem CID |
162642589
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
29
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| Heavy Atom Count |
89
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| Complexity |
2740
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)COCCOCCOCCNC(=O)C4=CC5=C(C=C4CS(=O)(=O)C)C6=CN(C(=O)C7=C6C(=CN7)CN5C8=C(C=C(C=N8)F)F)C)OC(=O)OC(C)C(C)SS(=O)(=O)C
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| InChi Key |
FUFQNGIGEJGHCG-YDIRMPGESA-N
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| InChi Code |
InChI=1S/C59H71F2N9O15S4/c1-33-51(86-32-66-33)37-12-10-36(11-13-37)24-65-55(73)47-22-41(85-58(76)84-34(2)35(3)87-89(9,79)80)28-70(47)57(75)52(59(4,5)6)67-48(71)30-83-19-18-82-17-16-81-15-14-62-54(72)42-23-46-43(20-38(42)31-88(8,77)78)44-29-68(7)56(74)50-49(44)39(25-63-50)27-69(46)53-45(61)21-40(60)26-64-53/h10-13,20-21,23,25-26,29,32,34-35,41,47,52,63H,14-19,22,24,27-28,30-31H2,1-9H3,(H,62,72)(H,65,73)(H,67,71)/t34?,35?,41-,47+,52-/m1/s1
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| Chemical Name |
[(3R,5S)-1-[(2S)-2-[[2-[2-[2-[2-[[8-(3,5-difluoropyridin-2-yl)-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carbonyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-5-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-3-yl] 3-methylsulfonylsulfanylbutan-2-yl carbonate
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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 : 200 mg/mL (152.38 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7619 mL | 3.8095 mL | 7.6190 mL | |
| 5 mM | 0.1524 mL | 0.7619 mL | 1.5238 mL | |
| 10 mM | 0.0762 mL | 0.3810 mL | 0.7619 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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