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| Targets |
BRD4 ligand-Linker Conjugate 1 TFA targets the bromodomain of Bromodomain-containing protein 4 (BRD4) [18L17-L18]. BRD4 is an epigenetic reader that binds to acetylated histones, regulating gene expression, and is a well-validated therapeutic target in cancer. This conjugate is not an active drug itself but a synthetic intermediate. The ligand portion binds to BRD4, while the linker is designed to connect this ligand to an E3 ubiquitin ligase ligand (not included in this conjugate) to form a complete PROTAC molecule [18L34-L36].
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| ln Vitro |
As a building block, BRD4 ligand-Linker Conjugate 1 TFA is not used for in vitro biological activity assays on its own. However, when incorporated into a full PROTAC molecule (e.g., by adding a Cereblon or VHL ligand), the resulting PROTAC will degrade BRD4 protein in cells. This leads to anti-proliferative effects in BRD4-dependent cancer cell lines, such as those derived from acute myeloid leukemia (AML), multiple myeloma, and certain solid tumors.
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| ln Vivo |
Detailed in vivo activity for this specific conjugate is not reported, as it is an intermediate. Its end-application in vivo is as part of a complete PROTAC molecule in xenograft mouse models of cancer. Such PROTACs have shown potent tumor growth inhibition by inducing sustained BRD4 degradation, which leads to downregulation of oncogenes like c-Myc. The conjugate serves as the BRD4-targeting warhead in these larger molecules.
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| Enzyme Assay |
The binding of the ligand portion of this conjugate to BRD4 can be assessed using non-cellular assays such as Surface Plasmon Resonance (SPR) or fluorescence polarization (FP). In these assays, the purified BRD4 bromodomain protein is immobilized, and the affinity of the small-molecule ligand for the bromodomain is measured. This serves as a quality control step to ensure the ligand retains its binding properties after conjugation to the linker. The linker portion of the molecule has no intrinsic binding activity.
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| Cell Assay |
Cellular experiments are not performed with the BRD4 ligand-Linker Conjugate alone. To use it in a cellular context, it must first be conjugated to an E3 ligase ligand (e.g., Thalidomide derivative for Cereblon or VHL ligand) to generate a functional PROTAC. The full PROTAC is then applied to cells, and BRD4 degradation is measured by Western blot to calculate DC₅0 values. Alternatively, a biotinylated version could be used for pull-down experiments.
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| Animal Protocol |
In vivo animal studies are not performed with the BRD4 ligand-Linker Conjugate 1 TFA alone. However, in the context of a complete PROTAC, in vivo studies are conducted using xenograft mouse models of cancer. For example, OPM-2 multiple myeloma cells or MOLM-13 AML cells are injected subcutaneously into immunodeficient mice. Once tumors are established, the BRD4-targeting PROTAC is administered intraperitoneally (IP) daily for several weeks. Efficacy is measured by tumor growth inhibition (TGI) and confirmed by Western blot analysis of tumor lysates to measure BRD4 degradation.
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| ADME/Pharmacokinetics |
PK data are not available for BRD4 ligand-Linker Conjugate 1 TFA alone. As a synthetic building block, its influence on the overall pharmacokinetic profile of the final PROTAC molecule is significant. The length and composition of the linker directly impact the molecular weight, solubility, permeability, and metabolic stability of the PROTAC. Linkers that are too short or too hydrophobic can lead to poor solubility and rapid clearance.
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| Toxicity/Toxicokinetics |
Toxicological data are not applicable to the isolated BRD4 ligand-Linker Conjugate 1 TFA, as it is not a therapeutic entity. The potential toxicity of the final PROTAC molecule is highly specific to its structure and target. For research use, the standard safety precautions for handling chemical compounds should be followed.
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| References |
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| Additional Infomation |
BRD4 ligand-Linker Conjugate 1 TFA (compound 106-1) has a molecular formula of C30H31ClF3N₇O2 and a molecular weight of 614.06 g/mol [19L4]. The non-TFA CAS number is 2154358-89-9 [6L27]. It appears as a light yellow to brown viscous liquid [6L27-L28]. It has a LogP of 3.9 and a tPSA (topological polar surface area) of 127 [6L17-L18]. For storage, it is typically kept at -20degC under an inert atmosphere to prevent degradation.
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| Molecular Formula |
C30H31CLF3N7O2
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| Molecular Weight |
614.06
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| Related CAS # |
BRD4 ligand-Linker Conjugate 1;2154358-89-9
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| Appearance |
Light yellow to brown viscous liquid
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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 (e.g. under nitrogen), 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) |
H2O :~100 mg/mL (~162.85 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 | 1.6285 mL | 8.1425 mL | 16.2851 mL | |
| 5 mM | 0.3257 mL | 1.6285 mL | 3.2570 mL | |
| 10 mM | 0.1629 mL | 0.8143 mL | 1.6285 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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