Antibodies
PHA-680632
- 貨號 Cat. No.
- S1454
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
PHA-680632
PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3. | |||||
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| Targets | Aurora A | Aurora B | Aurora C | |||
| IC50 | 27 nM | 135 nM | 120 nM [1] | |||
| In vitro | PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. PHA-680632 is selective for Aurora kinases, with 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, VEGFR2, and VEGFR3, and with IC50 higher than 10 μM for another 22 kinases. PHA-680632 shows 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) causes polyploidy in tumor cells. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. [1]PHA680632 in association with radiation leads 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 leads 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. [2] | |||||
| In vivo | HA-680632 (15–60 mg/kg) inhibits 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) suppresses 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. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Aurora Kinase Inhibition Assay | Inhibition of kinase activity by PHA-680632 is assessed using a scintillation proximity assay format. 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 M CsCl solution. In particular, a peptide derived from the Chocktide sequence (LRRWSLGL) is used as substrate for Aurora A, whereas the optimized peptide Auroratide is employed for Aurora B and C. The assay is run in a robotized format on 96-well plates. The potency of the compound toward Aurora kinases is evaluated and IC50 values are determined. |
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Cell Assay: [1]
| Cell lines | HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells |
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| Concentrations | 0.001-1 μM, dissolved in DMSO as 10 mM stock solution |
| Incubation Time | 72 hours |
| Method | Cells (5 × 103 to 1.5 × 104 per cm2) are seeded in 24-well plate. After 24 hours, plates are treated with PHA-680632 and incubated for 72 hours. At the end of incubation time, cells are detached from each plate and counted using a cell counter. IC50s are calculated using percentage of growth versus untreated cont |
Animal Study: [2]
| Animal Models | Mice (female athymic nude) xenografts models of p53−/− HCT116 cells |
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| Dosages | 40 mg/kg |
| Administration | Intraperitoneal (i.p.) injection twice a day |
| Solubility | 10% Tween 80, 30 mg/mL |
References
Chemical Information
| Molecular Weight (MW) | 501.62 |
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| Formula | C28H35N7O2 |
| CAS No. | 398493-79-3 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 10% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | N-(2,6-diethylphenyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)pyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-carboxamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.50162 | 5.0162 | 10.0324 | 15.0486 |
Customer Reviews (1)
 Click to enlarge | Rating | |
| Source | Dr. Zhang of Tianjin Medical University. PHA-680632 purchased from Selleck | |
| Method | Western blot | |
| Cell Lines | MDA-MB-231 cells | |
| Concentrations | 0-5 μM | |
| Incubation Time | ||
| Results | PHA-680632 treatment resulted in a reduction of Histone H3 and Aurora phosphorylation in MDA-MB-231 cells. |
Product Citations (4)
NEDD9 Depletion Destabilizes Aurora A Kinase and Heightens the Efficacy of Aurora A Inhibitors: Implications for Treatment of Metastatic Solid Tumors. [Ice RJ, et al. Cancer Res 2013;73(10):3168-80]
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res 2013;73(20):6310-22]
Proliferation State and Poloâ€Like Kinase1 Dependence of Tumorigenic Colon Cancer Cells. [Francescangeli F, et al. Stem Cells 2012;30(9):1819-30]
