PHA-680632 (Synonyms: Pha 680632) |
| Catalog No.GC10479 |
An Aurora kinase inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 398493-79-3
Sample solution is provided at 25 µL, 10mM.
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PHA-680632 is a novel and potent inhibitor of Aurora kinases, a small family of serine/threonine kinases regulating mitosis in chromosome segregation and cell division, that inhibits the activity of all three Aurora kinases with 50% inhibition concentration IC50 values of 27 nM, 135 nM and 120 nM for Aurora A, B and C kinases respectively. PHA-680632 also cross-reacts with other kinases, including FGFR1, FLT3, LCK, PLK1, STLK2, VEGFR2 and VEGFR3, to a lesser extent and exhibits much higher IC50 values (390 to 5500 nM) compared to Aurora kinases. Moreover, PHA-680632 potently inhibits proliferation in a wide range of cancer cell types, including HCT116, A2780, HL60 and Hela cells, with IC50 values ranging from 0.06 to 7.15 μM.
Reference
[1].Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9.
| Kinase experiment [1]: | |
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In vitro kinase assays |
Inhibition of kinase activity by PHA-680632 was assessed using a scintillation proximity assay format. In this assay, the biotinylated substrate is transphosphorylated by the kinase in presence of ATP traced with γ33-ATP. The phosphorylated substrate is then captured using streptavidin-coated scintillation proximity assay beads and the extent of phosphorylation is evaluated by β-counter after a 4-hour rest for the floatation of the beads on a dense 5 mol/L CsCl solution. In particular a peptide derived from the Chocktide sequence (LRRWSLGL) was used as substrate for Aurora A, whereas the optimized peptide Auroratide1 was employed for Aurora B and C. The assay was run in a robotized format on 96-well plates. The potency of the compound toward Aurora kinases and 29 additional kinases belonging to our Kinase Selectivity Screening panel was evaluated and the relevant IC50s were determined. |
| Cell experiment [1,2]: | |
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Cell lines |
HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.5 μM |
|
Applications |
PHA680632 in association with radiation led to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of PHA680632 (100–400 nM) prior to IR led to an enhancement of radiation-induced Annexin V positive cells, micronuclei formation, and Brca1 foci formation only in HCT116 cells with deficient p53, other than the p53 wild-type counterparts. PHA-680632 showed potent anti-proliferative effects in a wide range of cell types with IC50 values of 0.06–7.15 μM, including HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells. PHA-680632 (0.5 μM) caused polyploidy in tumor cells. |
| Animal experiment [1]: | |
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Animal models |
Mice xenografts models of HL60, A2780, and HCT116 cells, mouse mammary tumor virus v-Ha-ras transgenic mice |
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Dosage form |
Subcutaneous injection, 15–60 mg/kg |
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Application |
HA-680632 (15–60 mg/kg) inhibited tumor growth in mice xenografts models of HL60, A2780, and HCT116 cells, by reducing tumor cell proliferation and increasing apoptosis. PHA-680632 (45 mg/kg) suppressed growth of activated ras-driven mammary tumors in mouse mammary tumor virus v-Ha-ras transgenic mice and results in complete tumor stabilization and partial regression. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Soncini, C., Carpinelli, P., Gianellini, L., Fancelli, D., Vianello, P., Rusconi, L., ... & Ceruti, R. (2006). PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clinical Cancer Research, 12(13), 4080-4089. [2]. Tao, Y., Zhang, P., Frascogna, V., Lecluse, Y., Auperin, A., Bourhis, J., & Deutsch, E. (2007). Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. British Journal of Cancer, 97(12), 1664. |
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| Cas No. | 398493-79-3 | SDF | |
| Synonyms | Pha 680632 | ||
| Chemical Name | N-(2,6-diethylphenyl)-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carboxamide | ||
| Canonical SMILES | CCC1=C(C(=CC=C1)CC)NC(=O)N2CC3=C(C2)NN=C3NC(=O)C4=CC=C(C=C4)N5CCN(CC5)C | ||
| Formula | C28H35N7O2 | M.Wt | 501.62 |
| Solubility | ≥ 50.2 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9935 mL | 9.9677 mL | 19.9354 mL |
| 5 mM | 0.3987 mL | 1.9935 mL | 3.9871 mL |
| 10 mM | 0.1994 mL | 0.9968 mL | 1.9935 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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