| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
PNZ5 targets the bromodomains of BET family proteins, which include BRD2, BRD3, BRD4, and BRDT. These proteins are epigenetic readers that recognize acetylated lysines on histones and play a critical role in regulating gene transcription. By binding to the bromodomains, PNZ5 competitively displaces acetylated histones, thereby inhibiting the interaction of BET proteins with chromatin and suppressing the transcription of oncogenes such as c-MYC.
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| ln Vitro |
PNZ5 exhibits potent antiproliferative activity against various cancer cell lines in vitro. Studies have shown that it potently inhibits the growth of gastric cancer cells. Its activity is comparable to that of (+)-JQ1, a benchmark pan-BET inhibitor. The compound is used to study the effects of BET inhibition on cell proliferation, apoptosis, and gene expression.
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| ln Vivo |
In vivo, PNZ5 has demonstrated antitumor efficacy in preclinical models. As a pan-BET inhibitor, it has shown promise in treating various cancers, including gastric cancer. By inhibiting BET proteins, PNZ5 can reduce the expression of key oncogenes, leading to tumor growth inhibition. It is also being investigated for its potential in combination therapies.
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| Enzyme Assay |
The binding affinity of PNZ5 to BET bromodomains is typically evaluated using a fluorescence polarization (FP) or AlphaScreen assay. In these assays, a fluorescently labeled or tagged acetylated histone peptide is incubated with the target bromodomain and varying concentrations of PNZ5. The displacement of the peptide by PNZ5 results in a change in signal, from which the KD or IC50 is calculated.
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| Cell Assay |
Cellular assays are performed using cancer cell lines that are sensitive to BET inhibition. Cells are treated with PNZ5 at various concentrations for 72-96 hours. Cell viability is assessed using an ATP-based luminescence assay (CellTiter-Glo) or a colorimetric MTT assay. The IC50, representing the concentration required to inhibit cell growth by 50%, is then calculated.
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| Animal Protocol |
The in vivo efficacy of PNZ5 is evaluated in mouse xenograft models. Immunocompromised mice are implanted with human cancer cells, and once tumors are established, the animals are treated with PNZ5 via oral or intraperitoneal administration. Tumor volume is measured regularly, and the antitumor activity is assessed by comparing tumor growth in treated and control groups.
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| ADME/Pharmacokinetics |
PNZ5 has a molecular weight of 318.37 g/mol and a chemical formula of C20H18N2O2. It is soluble in DMSO. As a small molecule, it is expected to have good oral bioavailability. Pharmacokinetic studies in preclinical species would involve measuring plasma concentrations of the compound over time after administration to determine parameters like half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
PNZ5 is generally well-tolerated in preclinical studies at therapeutic doses. As a potent BET inhibitor, its toxicity is primarily related to its on-target effects, which can include impacts on normal cell proliferation and hematopoiesis. The safety profile is carefully evaluated in toxicology studies to determine the therapeutic window.
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| Additional Infomation |
PNZ5 is a research-grade small molecule used for signaling research. It is a specific isoxazole inhibitor developed as a potent alternative to (+)-JQ1. It is a valuable tool for studying the role of BET proteins in gene regulation and cancer biology, and for exploring new treatment options for diseases like gastric cancer.
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| Molecular Formula |
C20H18N2O2
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|---|---|
| Molecular Weight |
318.369124889374
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| Exact Mass |
318.136
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| CAS # |
1629277-36-6
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| PubChem CID |
78428091
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
476
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C(=NO1)C)C2=CC3=C(C=C2)C(=O)N([C@H]3C4=CC=CC=C4)C
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| InChi Key |
CHAKVDDAHQGTLR-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C20H18N2O2/c1-12-18(13(2)24-21-12)15-9-10-16-17(11-15)19(22(3)20(16)23)14-7-5-4-6-8-14/h4-11,19H,1-3H3/t19-/m0/s1
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| Chemical Name |
(3S)-5-(3,5-dimethyl-1,2-oxazol-4-yl)-2-methyl-3-phenyl-3H-isoindol-1-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.1410 mL | 15.7050 mL | 31.4100 mL | |
| 5 mM | 0.6282 mL | 3.1410 mL | 6.2820 mL | |
| 10 mM | 0.3141 mL | 1.5705 mL | 3.1410 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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