| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
The target is BRD4 (Bromodomain-containing protein 4). BRD4 recognizes and binds to acetylated lysine residues on histones, thereby recruiting transcriptional machinery to promote gene expression. It is involved in the expression of critical oncogenes like c-Myc and Bcl-2. BRD4 Inhibitor-20 competitively inhibits this binding to the acetylated histones.【15L10-L14】
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| ln Vitro |
Excellent BRD4 and BRD2 inhibitory action (BD1, IC50=19 nM; BD2, IC50=28 nM; BD1, IC50=24 nM; BD2, IC50=18 nM) is demonstrated by BRD4 Inhibitor-20 (compound 12j) [1]. C-Myc expression is decreased by BRD4 Inhibitor-20 (0.5, 2.5, and 5.0 μM; 24 hours) [1]. In HT-29, HL-60, and WI-38 cells, BRD4 Inhibitor-20 (72 h) has anti-proliferative effectiveness with IC50 values of 4.75 μM, 1.35 μM, and 44.07 μM, respectively[1]. HT-29 cells can be stopped from progressing through the cell cycle and going into the G1 phase by BRD4 Inhibitor-20 (2.5, 5.0, 10.0 μM; 24 h) [1].
BRD4 Inhibitor-20 has inhibitory activity against BRD4 BD1 and BD2 with IC50s of 19 nM and 28 nM, respectively. It demonstrates potent antiproliferative activity in a range of cancer cell lines, including colon cancer (e.g., Colo205), leukemia, and lymphoma. The compound is designed to block the expression of oncogenes such as c-Myc and to induce cell cycle arrest and apoptosis in cancer cells. |
| ln Vivo |
Compound 12j, also known as BRD4 Inhibitor-20, has good oral pharmacokinetic properties (iv, 5 mg/kg; po, 15 mg/kg) [1].
While specific in vivo data for this exact compound may not be widely published, it is described as an orally active inhibitor intended for pre-clinical research. In mouse xenograft models, BRD4 inhibitors typically show significant tumor growth inhibition. This compound is designed to be used in such models to evaluate its anti-cancer efficacy as a single agent or in combination with other therapies. |
| Enzyme Assay |
A biochemical assay for BRD4 is typically a time-resolved fluorescence resonance energy transfer (TR-FRET) or AlphaScreen assay. Recombinant BRD4 (BD1 or BD2) protein is incubated with a biotinylated acetylated histone H4 peptide and a donor/acceptor pair. Varying concentrations of BRD4 Inhibitor-20 are added to compete for binding. The decrease in signal is measured to calculate the IC50.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: HT-29 Cell Tested Concentrations: 0.5, 2.5, 5.0 μM Incubation Duration: 24 h Experimental Results: Significant inhibitory effect on c-Myc protein expression. Cell proliferation experiment [1] Cell Types: HT-29, HL-60, WI-38 Cell Tested Concentrations: Incubation Duration: 72 h Experimental Results: Strong anti-proliferative activity and weak toxicity. Cell cycle analysis[1] Cell Types: HT-29 Cell Line Tested Concentrations: 2.5, 5.0, 10.0 μM Incubation Duration: 24 hrs (hours) Experimental Results: Blocked cell cycle progression of cell line into G1 phase and percentage of cells in G1 phase 2.5, 5.0 and 10.0 The phases after treatment with μM concentration were 85.98%, 86.49% and 86.05% respectively. A cellular assay is performed in BRD4-dependent cancer cell lines, such as the colon cancer cell line Colo205 or the acute myeloid leukemia cell line MV4-11. Cells are treated with varying concentrations of BRD4 Inhibitor-20 for 72 hours. Cell viability is assessed using the CellTiter-Glo luminescent assay. The pharmacodynamic effect is confirmed by treating cells for 6-24 hours and then measuring the mRNA levels of the BRD4 target gene c-Myc by qRT-PCR and the protein levels of c-Myc by Western blot. |
| Animal Protocol |
Animal/Disease Models: Rat[1]
Doses: 5 mg/kg, 15 mg/kg Route of Administration: intravenous (iv) (iv)administration (iv) or oral administration (po) Experimental Results: PK parameters iv (5 mg/kg) po (15 mg/kg) Cmax (μg/L) - 2175 Tmax(h) - 1.00 t1/2(h) 1.56 3.59 CLz/F (L/h/kg) 0.68 1.03 AUC0−t(μg/L*h) 7296 14384 AUC0−∞(μg) /L*h) 7340 14600 F (%) - 66% No detailed in vivo protocols are available. A standard protocol for a BRD4 inhibitor involves establishing subcutaneous xenografts of Colo205 cells in female nude mice. When tumors reach a volume of ~100-150 mm3, the mice are randomized and treated with BRD4 Inhibitor-20 (e.g., 50-100 mg/kg) or vehicle by oral gavage once or twice daily. Tumor volumes are measured with calipers every 2-3 days. Tumors are harvested at the end of the study for IHC analysis of Ki-67 and cleaved caspase-3. |
| ADME/Pharmacokinetics |
Specific quantitative pharmacokinetic parameters for BRD4 Inhibitor-20 are not detailed in the available literature. However, the compound is characterized as "orally active," which implies it has sufficient oral bioavailability, metabolic stability, and systemic exposure to exert in vivo efficacy. Its structure is likely optimized for these properties.
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| Toxicity/Toxicokinetics |
Specific toxicological data for BRD4 Inhibitor-20 are not provided. As an inhibitor of an epigenetic regulator with broad effects on gene expression, on-target toxicities such as gastrointestinal distress and bone marrow suppression are potential concerns, similar to other BET inhibitors. However, such data would be generated during pre-clinical toxicology studies.
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| References | |
| Additional Infomation |
BRD4 is a validated target in cancer, with several inhibitors having progressed to clinical trials. BRD4 Inhibitor-20 is a research-grade chemical for pre-clinical studies. As of the latest updates, it has not been evaluated in clinical trials or been approved for sale. It is a pre-clinical research tool for oncology target validation and early drug discovery.
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| Molecular Formula |
C18H18N2O4S
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| Molecular Weight |
358.411523342133
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| Exact Mass |
358.098
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| CAS # |
2490311-14-1
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| PubChem CID |
162653363
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
649
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(S(NC2C=CC3=C(C=2)/C(=C(/C)\C)/C(=O)N3)(=O)=O)=CC=CC=C1OC
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| InChi Key |
CDERLIUJSXSXFH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18N2O4S/c1-11(2)17-13-10-12(8-9-14(13)19-18(17)21)20-25(22,23)16-7-5-4-6-15(16)24-3/h4-10,20H,1-3H3,(H,19,21)
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| Chemical Name |
2-methoxy-N-(2-oxo-3-propan-2-ylidene-1H-indol-5-yl)benzenesulfonamide
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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 : ~125 mg/mL (~348.76 mM)
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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 | 2.7901 mL | 13.9505 mL | 27.9010 mL | |
| 5 mM | 0.5580 mL | 2.7901 mL | 5.5802 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7901 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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