Size | Price | Stock | Qty |
---|---|---|---|
1mg |
|
||
5mg |
|
||
10mg |
|
||
Other Sizes |
|
Phthalazinone pyrazole is a novel potent inhibitor of Aurora A kinase with IC50 of 31 nM. It does not inhibit Aurora B kinase at doses up to 100 μM. Phthalazinone pyrazole inhibits the proliferation of HCT116, COLO 205, and MCF-7 cells (IC50 = 7.8, 2.9, and 1.6 μM, respectively).
ln Vitro |
Western blotting and qPCR confirmed that phthalazinonepyrazol (1 and 10 μM; 30 hours) increases HLC proliferation, while phelanonepyrazole (1, 10 and 100 μM; 5 days) improves liver morphological changes in differentiated HLC without cytotoxicity. Phthalazinonepyrazol (1 and 10 μM; 5 and 17 days) inhibits EMT and induces HLC maturation by upregulating HNF4α while inhibiting the AKT signaling pathway through off-target effects, rather than directly inhibiting Aurora-A.
|
---|---|
Cell Assay |
Cell proliferation assay [2]
Cell Types: Hepatocyte-like cells (HLC) Tested Concentrations: 1 and 10 μM Incubation Duration: 30 hrs (hours) Experimental Results: The proliferation ability of HLC was enhanced. Cytotoxicity assay [2] Cell Types: ES-HLC, iPS-HLC, Huh7 Cell Tested Concentrations: 1, 10 and 100 μM Incubation Duration: 5 days Experimental Results: No cytotoxic effect on HLC. Western Blot Analysis[2] Cell Types: HLC Tested Concentrations: 1 and 10 μM Incubation Duration: 5 and 17 days Experimental Results: Dramatically inhibited AKT phosphorylation and activated GSK-3β, which in turn inhibited Snail expression and increased HNF4α. Phthalazinopyrazole did not Dramatically reduce the phosphorylation of Aurora-A. RT-PCR[2] Cell Types: HLC Tested Concentrations: 1 and 10 μM Incubation Duration: 5 and 17 days Experimental Results: Dramatically inhibited AKT mRNA phosphorylation and activated GSK-3β mRNA, thereby inhibiting Snail mRNA expression and increasing HNF4α mRNA. Phthalazinopyrazole did not Dramatically reduce the phosphorylation of Aurora-A mRNA. |
References |
[1]. Prime ME, et al. Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase. J Med Chem. 2011;54(1):312-319.
[2]. Choi YJ, et al. Phthalazinone Pyrazole Enhances the Hepatic Functions of Human Embryonic Stem Cell-Derived Hepatocyte-Like Cells via Suppression of the Epithelial-Mesenchymal Transition. Stem Cell Rev Rep. 2018;14(3):438-450. |
Molecular Formula |
C18H15N5O
|
---|---|
Molecular Weight |
317.344602823257
|
Exact Mass |
317.13
|
Elemental Analysis |
C, 68.13; H, 4.76; N, 22.07; O, 5.04
|
CAS # |
880487-62-7
|
Related CAS # |
880487-62-7;
|
Appearance |
Solid powder
|
SMILES |
CC1=CC(=NN1)NC2=NN(C(=O)C3=CC=CC=C32)C4=CC=CC=C4
|
Synonyms |
Phthalazinone pyrazole
|
HS Tariff Code |
2934.99.9001
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
DMSO : ≥ 11.11 mg/mL (~35.01 mM)
|
---|---|
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 | 3.1512 mL | 15.7560 mL | 31.5119 mL | |
5 mM | 0.6302 mL | 3.1512 mL | 6.3024 mL | |
10 mM | 0.3151 mL | 1.5756 mL | 3.1512 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.