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Purity: ≥98%
| Targets |
ZL0454 targets Bromodomain-Containing Protein 4 (BRD4), a member of the bromodomain and extraterminal (BET) family of proteins. BRD4 binds to acetylated lysine residues on histones and regulates gene transcription. By inhibiting the bromodomains of BRD4, ZL0454 blocks the interaction between BRD4 and acetylated chromatin, thereby modulating gene expression. The compound has IC50 values of 49 nM for BRD4-BD1 and 32 nM for BRD4-BD2.
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| ln Vitro |
In vitro, ZL0454 is a potent and highly selective BRD4 inhibitor with IC50 values of 49 nM for BRD4-BD1 and 32 nM for BRD4-BD2. It has nanomolar binding affinities to the bromodomains of BRD4. The compound is an analog of ZL0420 and is used in research related to cancer and transcriptional regulation. Specific cellular assay data, such as IC50 values for inhibition of cell proliferation, are not detailed in the available sources.
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| ln Vivo |
Specific in vivo activity data for ZL0454 are not detailed in the available sources. As a potent and selective BRD4 inhibitor, the compound is expected to have in vivo activity in cancer models. BRD4 inhibitors are known to have antitumor activity in various cancers. However, specific animal model studies have not been described in the available literature. The compound is intended for research use only.
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| Enzyme Assay |
The BRD4 binding assay for ZL0454 involves incubating the compound with recombinant BRD4 bromodomains (BD1 and BD2) and a fluorescently labeled acetylated histone peptide. The binding affinity is measured using a fluorescence polarization or TR-FRET assay. IC50 values for displacement of the labeled peptide are calculated. The compound's selectivity can be assessed by testing against other bromodomain-containing proteins.
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| Cell Assay |
To evaluate the cellular activity of ZL0454, cancer cell lines (such as those sensitive to BET inhibition) are seeded in 96-well plates and treated with varying concentrations of ZL0454. Cell proliferation is measured using an MTT or CellTiter-Glo assay after 72 hours of treatment. The IC50 for inhibition of cell proliferation is calculated. BRD4 target gene expression (such as MYC) is measured by quantitative RT-PCR. BRD4 chromatin occupancy can be assessed by ChIP-seq.
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| Animal Protocol |
Specific in vivo animal experiment protocols for ZL0454 are not detailed in the available sources. As a BRD4 inhibitor, the compound would typically be evaluated in xenograft models using human cancer cell lines implanted subcutaneously into immunodeficient mice. ZL0454 would be administered orally or intraperitoneally, and tumor growth inhibition would be measured. However, specific protocols are not described in the available literature.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for ZL0454 are not provided in the available sources. The compound has a molecular weight of 374.46 and a molecular formula of C18H22N4O3S. It is a small molecule with properties suitable for oral administration. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS to determine key PK parameters.
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| Toxicity/Toxicokinetics |
Specific toxicity data for ZL0454 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and selective BRD4 inhibitor, and its toxicity profile would be expected to be consistent with other BET inhibitors. Standard safety precautions should be followed when handling this compound.
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| References |
:Am J Respir Cell Mol Biol.2018 Aug 28. doi: 10.1165/rcmb.2017-0445OC;Eur J Med Chem.2018 May 10;151:450-461.
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| Additional Infomation |
ZL0454 is a potent and highly selective BRD4 inhibitor with IC50 values of 49 nM and 32 nM for BRD4-BD1 and BRD4-BD2, respectively. It is an analog of ZL0420 and has nanomolar binding affinities to the bromodomains of BRD4. The compound has a molecular formula of C18H22N4O3S and a molecular weight of 374.46.
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| Molecular Formula |
C18H22N4O3S
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| Molecular Weight |
374.457282543182
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| Exact Mass |
374.141
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| CAS # |
2229042-77-5
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| Related CAS # |
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| PubChem CID |
137285009
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
578
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=CC=1)/N=N/C1C=C(C)C(=CC=1N)O)(NC1CCCC1)(=O)=O
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| InChi Key |
IRKMSULWLDLTIK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H22N4O3S/c1-12-10-17(16(19)11-18(12)23)21-20-13-6-8-15(9-7-13)26(24,25)22-14-4-2-3-5-14/h6-11,14,22-23H,2-5,19H2,1H3
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) 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. 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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 | 2.6705 mL | 13.3526 mL | 26.7051 mL | |
| 5 mM | 0.5341 mL | 2.6705 mL | 5.3410 mL | |
| 10 mM | 0.2671 mL | 1.3353 mL | 2.6705 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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