Danusertib (PHA-739358)
(Synonyms: 达鲁舍替,5-Amido-pyrrolopyrazole 9d) 目录号 : GC15217
A pan-Aurora kinase and Abl inhibitor
Cas No.:827318-97-8
Sample solution is provided at 25 µL, 10mM.
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Danusertib (previously known as PHA-739358), a 3-aminopyrazole derivative identified during the development of the pyrrolopyrazole sub-series, is a potent small-molecule inhibitor of aurora kinases family members with a dominant inhibition for aurora B kinase (ABK). This pan-aurora kinases inhibitor is also able to inhibit several tyrosine kinases, including T315I mutant, Ret, Trk-A and fibroblast growth factor receptor-1 (FGFR-1), which are involved in multiple malignancies, such as chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), thyroid prostate and breast carcinoma. Thus, in many previous studies, danusertib exhibits remarkable antitumor activity in a number of different xengorafts, spontaneous, and transgenic animal tumor models with a favorable pharmacokinetic and safety profile.
Reference
[1].Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, Moll J. PHA-739358, a potent inhibitor of aurora kinases with a selecyive target inhibiton profile relevant to cancer. Mol Cancer Ther 2007; 6(12 Pt 1): 3158-3168
| Kinase experiment [1]: | |
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Biochemical kinase assays |
The Km values for ATP and the specific substrate were initially determined, and each assay was then run at optimized ATP (2Km) and substrate (5Km) concentrations. This setting enabled direct comparison of IC50 values of Danusertib across the applied kinase selectivity screening panel for the evaluation of the selectivity profile. |
| Cell experiment [2]: | |
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Cell lines |
CD34+ 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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
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Reaction Conditions |
5 μM; 5 days |
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Applications |
In CD34+ cells from an IM-resistant CML patient, Danusertib induced apoptosis and reduced phosphorylation of P-CrkL. |
| Animal experiment [2]: | |
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Animal models |
Female SCID mice s.c. injected with K562 cells |
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Dosage form |
15 mg/kg; i.p.; b.i.d., for 10 days |
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Applications |
Danusertib significantly inhibited K562 cell proliferation and virtually suppressed tumor growth. |
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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]. Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, Moll J. PHA-739358, a potent inhibitor of aurora kinases with a selecyive target inhibiton profile relevant to cancer. Mol Cancer Ther 2007; 6(12 Pt 1): 3158-3168. [2]. Gontarewicz A, Balabanov S, Keller G, Colombo R, Graziano A, Pesenti E, Benten D, Bokemeyer C, Fiedler W, Moll J, Brümmendorf TH. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood. 2008 Apr 15;111(8):4355-64. | |
| Cas No. | 827318-97-8 | SDF | |
| 别名 | 达鲁舍替,5-Amido-pyrrolopyrazole 9d | ||
| 化学名 | N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide | ||
| Canonical SMILES | CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC4=C3CN(C4)C(=O)C(C5=CC=CC=C5)OC | ||
| 分子式 | C26H30N6O3 | 分子量 | 474.55 |
| 溶解度 | ≥ 23.75 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 | 2.1073 mL | 10.5363 mL | 21.0726 mL |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet