| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
PROTAC BRD4 ligand-1 targets BRD4 (bromodomain-containing protein 4), a member of the BET (bromodomain and extraterminal) protein family. BRD4 is a transcriptional regulator that recognizes acetylated lysine residues on histones via its bromodomains and recruits transcriptional machinery to promote gene expression. It is implicated in various cancers and inflammatory diseases. As a BET inhibitor and BRD4 ligand, PROTAC BRD4 ligand-1 binds to BRD4 and can be used to recruit E3 ubiquitin ligases for targeted protein degradation in PROTAC molecules.
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| ln Vitro |
In vitro, PROTAC BRD4 ligand-1 is a potent BET inhibitor and a ligand for the BRD4 protein. It can be used to prepare PROTAC GNE-987, a heterobifunctional molecule that induces degradation of BRD4. The compound's ability to bind BRD4 with high affinity makes it a valuable tool for studying BRD4 biology and for developing targeted protein degradation strategies. As a BET inhibitor, it also has intrinsic activity in blocking BRD4-mediated transcription.
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| ln Vivo |
In vivo, PROTAC BRD4 ligand-1 is used as a building block for PROTAC molecules such as GNE-987, which induce targeted degradation of BRD4. BRD4 degradation has been shown to have antitumor activity in various cancer models. However, specific in vivo efficacy data for the ligand alone have not been detailed in the available literature. The compound's primary use is in the synthesis of PROTAC molecules for research into targeted protein degradation.
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| Enzyme Assay |
For in vitro binding assays, recombinant BRD4 bromodomain proteins are incubated with fluorescently labeled or radiolabeled ligands at various concentrations of PROTAC BRD4 ligand-1 (0.1-1000 nM). Binding affinity (Kd) is determined using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or fluorescence polarization assays. IC50 values for BET inhibition are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, cancer cells are treated with PROTAC BRD4 ligand-1 or with PROTAC molecules synthesized using this ligand (such as GNE-987) at concentrations ranging from 0.01-10 µM. BRD4 protein levels are assessed by Western blotting to confirm degradation. Cell viability and proliferation are measured using CellTiter-Glo or MTT assays. Gene expression changes can be assessed by RNA-seq or qRT-PCR to evaluate the effects of BRD4 inhibition or degradation.
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| Animal Protocol |
For in vivo studies, PROTAC molecules synthesized from PROTAC BRD4 ligand-1 (such as GNE-987) would be administered to tumor-bearing mice. BRD4 degradation in tumors would be confirmed by Western blotting. Tumor growth inhibition would be assessed. However, specific in vivo protocols for the ligand itself have not been detailed. The compound is primarily used as a synthetic intermediate for PROTAC research.
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| ADME/Pharmacokinetics |
PROTAC BRD4 ligand-1 is soluble in DMSO at 5 mg/mL. Storage is recommended at -20°C for long-term stability. The compound is for research use only and is not intended for human or veterinary use. Standard laboratory safety precautions should be followed when handling this compound.
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| Toxicity/Toxicokinetics |
Toxicological data for PROTAC BRD4 ligand-1 have not been extensively reported, as it is a research reagent for PROTAC synthesis rather than a therapeutic agent. Standard laboratory safety precautions should be followed when handling this compound. It is not intended for human use.
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| References | |
| Additional Infomation |
PROTAC BRD4 ligand-1 is a potent BET inhibitor and a ligand targeting BRD4 for use in PROTAC molecules such as GNE-987. It is an essential building block for chemical biology and drug discovery in epigenetics and targeted protein degradation. PROTAC BRD4 ligand-1 is a research tool and is not approved for clinical use.
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| Molecular Formula |
C23H18F2N4O5S
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|---|---|
| Molecular Weight |
500.474630832672
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| Exact Mass |
500.096
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| CAS # |
2313230-51-0
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| PubChem CID |
142572767
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C)(CC1C(C(=O)O)=CC2=C(C=1)C1=CN(C)C(C3=C1C(=CN3)CN2C1C(=CC(=CN=1)F)F)=O)(=O)=O
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| InChi Key |
BSYGSSMAXOMCQE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H18F2N4O5S/c1-28-9-16-15-3-11(10-35(2,33)34)14(23(31)32)5-18(15)29(21-17(25)4-13(24)7-27-21)8-12-6-26-20(19(12)16)22(28)30/h3-7,9,26H,8,10H2,1-2H3,(H,31,32)
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| Chemical Name |
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-carboxylic 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 |
| 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 : ~5 mg/mL (~9.99 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.00 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 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 | 1.9981 mL | 9.9906 mL | 19.9812 mL | |
| 5 mM | 0.3996 mL | 1.9981 mL | 3.9962 mL | |
| 10 mM | 0.1998 mL | 0.9991 mL | 1.9981 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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