PHA-680632
(Synonyms: Pha 680632) 目录号 : GC10479
An Aurora kinase inhibitor
Cas No.:398493-79-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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. |
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Reacting condition |
0.5 μM |
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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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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.
| Cas No. | 398493-79-3 | SDF | |
| 别名 | Pha 680632 | ||
| 化学名 | 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 | ||
| 分子式 | C28H35N7O2 | 分子量 | 501.62 |
| 溶解度 | ≥ 50.2 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。