AZD1152(Barasertib)

製品コードS1051 バッチS105102

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H31FN7O6P
分子量 587.54 CAS No. 722543-31-9
Solubility (25°C)* 体外 DMSO 118 mg/mL (200.83 mM)
Water 118 mg/mL (200.83 mM)
Ethanol 3 mg/mL (5.1 mM)
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AZD1152は、Aurora Bの選択的阻害剤であり、Kiは0.36 nMです。
in vitro AZD1152 (Barasertib) is a pro-drug converting to active substance AZD1152-HQPA in human plasma, which inhibits Aurora-A, Aurora B-INCENP, and Aurora C-INCENP with Kis of 687 nM, 0.36 nM, and 17.0 nM, indicating a 100-fold selectivity for Aurora-B over Aurora-A. This compound results in a dose-dependent inhibition of histone H3 phosphorylation on Ser10 in SW620 colorectal tumor cell line. It induces growth arrest of a variety of types of leukemia cells, with IC50 of 5, 12, and 8 nM for ALL PALL-2, MOLM13, MV4-11 respectively.
in vivo AZD1152 (Barasertib) (2.5 mg/kg/d) significantly suppresses PhH3 by 69% in SW620 colon tumors. It (10-150 mg/kg/d) inhibits growth in a panel of human tumor xenografts including Colo205, A549, and HL-60 with inhibition rate ranging from 55% to 100%. Additional results show cells exposed to this compound end up apoptosis. It (25 mg/kg) markedly suppresses the growth and weights of AZD1152-treated tumors in MOLM13 xenografts.
特徴 Selectivity for Aurora-B over Aurora-A.

プロトコル(参考用のみ)

キナーゼアッセイ Affinity determination
AZD1152 (Barasertib) is incubated with Aurora A or Aurora B-INCENP and the substrate peptide. Twenty microliters of reaction mix (25 mM Tris-HCl, 12.7 mM KCl, 2.5 mM NaF, 0.6 mM dithiothreitol, 6.25 mM MnCl2, 7.5μM ATP for Aurora A assay and 15 μM for Aurora B-INCENP assay, 6.25 μM peptide substrate containing 0.2 μCi [γ33P]ATP) is then added to all test wells to start the reaction (to give a final volume of 50 μL). Plates are incubated at room temperature for 60 min, reactions are stopped by addition of 100 μL of 20% v/v orthophosphoric acid, and peptide substrate is captured on positively charged nitrocellulose P30 filtermat using a 96-well plate harvester and then assayed for incorporation of 33P with a Beta plate counter.
細胞アッセイ 細胞株 ALL PALL-2; MOLM13; MV4-11 cells
濃度 ~100 nM
反応時間 48 h
実験の流れ Leukemic cells are grown in liquid culture for 2 days in the presence of various concentrations of AZD1152-HQPA (1-100 nM), which is the active metabolite of AZD1152 (Barasertib). Growth inhibition is measured by thymidine uptake; the percent inhibition is graphed and the concentration of this compound that induced 50% growth inhibition (IC50) of leukemia cells is determined.
動物実験 動物モデル Male nude mice bearing SW620, Colo205, A549, and HL-60 human tumor xenografts.
投薬量 2.5-150 mg/kg
投与方法 i.v. i.p. s.c.

参考

  • http://www.aacr.org/home/scientists/meetings--workshops/molecular-targets-and-cancer-therapeutics/previous-molecular-targets-and-cancer-therapeutics-conferences/2005-molecular-targets-and-cancer-therapeutics/proceedings.aspx
  • http://www.ncbi.nlm.nih.gov/pubmed?term=17575233
  • http://www.ncbi.nlm.nih.gov/pubmed?term=17495131
  • http://www.ncbi.nlm.nih.gov/pubmed?term=17373783

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Rsk2 and Lrp5 deficiency limit osteosarcoma growth in cFos-transgenic mice by different mechanisms [ ProQuest , 2023, 30683696] PubMed: None
Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib [Ivanova D, et al. Anticancer Res, 2018, 38(3):1407-1414] PubMed: 29491065
Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents [Jayanthan A, et al. PLoS One, 2014, 9(7):e102741] PubMed: 25048812
Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death. [Ratushny V, et al. Oncogene, 2012, 31(10):1217-27] PubMed: 21785464
Aurora B is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway and is a valuable potential target in melanoma cells. [Bonet C, et al. J Biol Chem, 2012, 287(35):29887-98] PubMed: 22767597
Preclinical Characterization of ABT-348, a Kinase Inhibitor Targeting the Aurora, Vascular Endothelial Growth Factor Receptor/Platelet-Derived Growth Factor … [Glaser KB, et al. J Pharmacol Exp Ther, 2012, 343(3):617-27] PubMed: 22935731
Aurora A and Aurora B jointly coordinate chromosome segregation and anaphase microtubule dynamics. [H間arat N, et al. J Cell Biol, 2011, 195(7):1103-13] PubMed: 22184196

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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