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| 5mg |
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| Targets |
iBRD4-BD1 diTFA selectively targets the first bromodomain (BD1) of the bromodomain-containing protein 4 (BRD4). BRD4 is an epigenetic reader protein that recognizes acetylated lysine residues on histones and plays a critical role in regulating gene transcription. It is involved in the expression of oncogenes such as MYC and is a validated therapeutic target in cancer and inflammatory diseases.
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| ln Vitro |
iBRD4-BD1 diTFA has affinity and selectivity for BET series BRD4-BD1 with an IC50 value of 12 nM[1]. iBRD4-BD1 diTFA has affinity and selectivity for BET series BRD4-BD2, BRD3-BD1, BRD3-BD2, BRD2-BD1 and BRD2-BD2 with IC50 values of 16 μM, 1.0 μM, 75 μM, 80 nM and 7.1 μM, respectively[1]. iBRD4-BD1 (0-50 μM; 72 h) diTFA is cytotoxic in MM.1S cells with an EC50 value of 2.3 μM[1].
In vitro, iBRD4-BD1 diTFA shows affinity and selectivity for BRD4-BD1 with an IC50 of 12 nM. For other bromodomains, the IC50 values are: 16 μM for BRD4-BD2, 1.0 μM for BRD3-BD1, 75 μM for BRD3-BD2, 80 nM for BRD2-BD1, and 7.1 μM for BRD2-BD2. This demonstrates significant selectivity for BD1 over other bromodomains. The compound exhibits cytotoxicity in MM.1S cells with an EC50 of 2.3 μM (72-hour treatment, 0-50 μM range). |
| ln Vivo |
In vivo activity of iBRD4-BD1 diTFA has been evaluated in preclinical models of inflammation and oncology. As a BRD4 inhibitor, it can suppress the transcription of oncogenes and inflammatory genes, leading to reduced tumor growth and inflammation. Detailed in vivo efficacy data, including effects in xenograft models and inflammatory disease models, are available in the primary literature. The compound's selectivity for BD1 over BD2 may provide a differentiated therapeutic profile.
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| Enzyme Assay |
Non-cellular binding assays for iBRD4-BD1 diTFA involve competitive binding studies using fluorescence polarization (FP) or AlphaScreen technology. Purified bromodomain proteins (BRD4-BD1, BRD4-BD2, BRD2-BD1, BRD2-BD2, BRD3-BD1, BRD3-BD2) are incubated with a fluorescently labeled acetylated histone peptide ligand and varying concentrations of the test compound. The displacement of the labeled ligand is measured, and IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular experiments with iBRD4-BD1 diTFA are conducted in cancer cell lines such as MM.1S multiple myeloma cells. Cells are treated with the compound at various concentrations, and cell viability is assessed using assays such as CellTiter-Glo or MTT after 72 hours of treatment. Cytotoxicity is quantified by calculating EC50 values. Additional cellular assays may include measuring BRD4 target gene expression (e.g., MYC) by qPCR and assessing cell cycle distribution or apoptosis induction.
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| Animal Protocol |
In vivo animal studies for iBRD4-BD1 diTFA are performed in murine xenograft models using cancer cell lines sensitive to BRD4 inhibition. The compound is administered via appropriate routes (e.g., oral, intraperitoneal) at various dose levels. Tumor growth is monitored, and endpoints include tumor volume measurements, survival analysis, and pharmacodynamic assessments of target engagement and gene expression changes in tumor tissues. Efficacy is compared to vehicle controls and reference compounds.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of iBRD4-BD1 diTFA include a molecular weight of 749.62 and a molecular formula of C33H32F9N5O5. The CAS number is 2839318-20-4. The compound is stored as a powder at -20°C for up to 3 years and in solution at -80°C for 1 year. For in vivo administration, formulations may include DMSO, PEG300, Tween 80, and saline. The diTFA salt form enhances aqueous solubility compared to the free base.
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| Toxicity/Toxicokinetics |
Toxicity data for iBRD4-BD1 diTFA are generated during preclinical development. As a bromodomain inhibitor targeting epigenetic regulators, potential toxicities may include effects on normal tissues with high BRD4 dependence. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions for research use only.
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| References | |
| Additional Infomation |
iBRD4-BD1 diTFA is a research compound supplied for preclinical studies only, not for human therapeutic use. It is identified by the SMILES structure provided in the supplier's documentation. The compound shows selectivity for BRD4-BD1 over other bromodomains and can be used for inflammation and oncology research. Other forms of the compound may be available for different research applications.
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| Molecular Formula |
C33H32F9N5O5
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| Molecular Weight |
749.62
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| Exact Mass |
749.226
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| CAS # |
2839318-20-4
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| PubChem CID |
169494549
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| Appearance |
Colorless to light yellow viscous liquid
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
52
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| Complexity |
824
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)C(C)C)OC2=NC=CC(=N2)C3=C(N=CN3C4CCNCC4)C5=CC=C(C=C5)C(F)(F)F.C(=O)(C(F)(F)F)O.C(=O)(C(F)(F)F)O
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| InChi Key |
GUUBIJTYNCEMRN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H30F3N5O.2C2HF3O2/c1-18(2)21-5-4-19(3)25(16-21)38-28-34-15-12-24(36-28)27-26(20-6-8-22(9-7-20)29(30,31)32)35-17-37(27)23-10-13-33-14-11-23;2*3-2(4,5)1(6)7/h4-9,12,15-18,23,33H,10-11,13-14H2,1-3H3;2*(H,6,7)
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| Chemical Name |
2-(2-methyl-5-propan-2-ylphenoxy)-4-[3-piperidin-4-yl-5-[4-(trifluoromethyl)phenyl]imidazol-4-yl]pyrimidine;bis(2,2,2-trifluoroacetic acid)
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~100 mg/mL (~133.40 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.34 mM) 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; with ultrasonication.
For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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: 2.5 mg/mL (3.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 1.3340 mL | 6.6700 mL | 13.3401 mL | |
| 5 mM | 0.2668 mL | 1.3340 mL | 2.6680 mL | |
| 10 mM | 0.1334 mL | 0.6670 mL | 1.3340 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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