PF-03814735
(Synonyms: N-[2-[(1S,4R)-6-[[4-(环丁基氨基)-5-(三氟甲基)-2-嘧啶基]氨基]-1,2,3,4-四氢萘-1,4-亚氨-9-基]-2-氧代乙基]乙酰胺) 目录号 : GC18074
PF-03814735 是一种有效的、具有口服生物利用度的 Aurora1 和 Aurora2 激酶的可逆抑制剂，IC50 值分别为 0.8nM 和 5nM 。
Cas No.:942487-16-3
Sample solution is provided at 25 µL, 10mM.
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PF-03814735 is a potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases with IC50 values of 0.8nM and 5nM, respectively [1].
PF-03814735 is an ATP competitive inhibitor of Aurora kinases. It also shows inhibition of other protein kinases at 100nM, such as Flt1, FAK, TrkA, Met, and FGFR1. The immunofluorescence imaging analysis shows PF-03814735 can inhibit the phosphorylation of Aurora1, Aurora 2 as well as histone H3 in MDA-MB-231 cells. This inhibition is rapid and reversible. The inhibition of phosphorylated histone H3 also occurs in athymic mice bearing HCT-116 xenografts. PF-03814735 induces the formation of polyploid cells and multinucleated cells due to the block in cytokinesis secondary. Moreover, PF-03814735 treatment results in a reduction of cell proliferation in vitro (such as HL-60, A549, and H125) and a inhibition of tumor growth in vivo (human xenograft mouse models, such as A2780 ovarian carcinoma and HCT-116) [1].
References:
[1] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.
PF-03814735 是一种有效的、具有口服生物利用度的 Aurora1 和 Aurora2 激酶的可逆抑制剂，IC50 值分别为 0.8nM 和 5nM [1]。
PF-03814735 是一种 ATP 竞争性抑制剂极光激酶。它还显示在 100nM 时抑制其他蛋白激酶，例如 Flt1、FAK、TrkA、Met 和 FGFR1。免疫荧光成像分析表明，PF-03814735 可以抑制 MDA-MB-231 细胞中 Aurora1、Aurora 2 以及组蛋白 H3 的磷酸化。这种抑制是快速和可逆的。磷酸化组蛋白 H3 的抑制也发生在携带 HCT-116 异种移植物的无胸腺小鼠中。由于继发性胞质分裂受阻，PF-03814735 诱导多倍体细胞和多核细胞的形成。此外，PF-03814735 治疗导致体外细胞增殖减少（如 HL-60、A549 和 H125）和抑制体内肿瘤生长（人异种移植小鼠模型，如 A2780 卵巢癌和 HCT-116 ) [1].
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 cells, various tumor types (HCT-116, HL-60, A549, and H125) as well as tumor cell lines of rat (C6), mouse (L1210), and dog (MDCK) origin. |
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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 |
1-1000 nM; 4, 8, 12, 24, and 48 h |
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Applications |
In MDA-MB-231 cells, PF-03814735 markedly reduced levels of Aurora1 phosphorylated on Thr 232 and the phosphorylation of histone H3 on Ser10 with IC50 values of 20 nmol/L and 50 nmol/L. In various tumor cell lines, PF-03814735 resulted in a reduction in cell number with IC50 values ranging from 42 to 150 nmol/L. PF-03814735 at 300 nmol/L produced near-complete inhibition of cell proliferation. |
| Animal experiment [1]: | |
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Animal models |
Athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts |
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Dosage form |
10, 20, and 30 mg/kg; oral gavage for 10 days |
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Application |
In athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts, PF-03814735 (≥20 mg/kg) resulted in statistically significant and dose-dependent tumor growth inhibition of ≥50% relative to vehicle-treated mice. The tumor growth inhibition was associated with a reduction in phosphorylated histone H3 levels of ≥50% for approximately 5 hours each day for 10 days. |
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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] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94. |
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| Cas No. | 942487-16-3 | SDF | |
| 别名 | N-[2-[(1S,4R)-6-[[4-(环丁基氨基)-5-(三氟甲基)-2-嘧啶基]氨基]-1,2,3,4-四氢萘-1,4-亚氨-9-基]-2-氧代乙基]乙酰胺 | ||
| Canonical SMILES | CC(=O)NCC(=O)N1C2CCC1C3=C2C=CC(=C3)NC4=NC=C(C(=N4)NC5CCC5)C(F)(F)F | ||
| 分子式 | C23H25F3N6O2 | 分子量 | 474.48 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 16 mg/ml,Ethanol: 20 mg/ml,Ethanol:PBS (pH 7.2) (1:9): 0.10 mg/ml | 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 | 2.1076 mL | 10.5379 mL | 21.0757 mL |
| 5 mM | 0.4215 mL | 2.1076 mL | 4.2151 mL |
| 10 mM | 0.2108 mL | 1.0538 mL | 2.1076 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。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet