PHA-680632

製品コードS1454 バッチS145403

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

C28H35N7O2
分子量 501.62 CAS No. 398493-79-3
Solubility (25°C)* 体外 DMSO 100 mg/mL (199.35 mM)
Water Insoluble
Ethanol Insoluble
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 PHA-680632は、Aurora A、Aurora B、およびAurora Cの強力な阻害剤であり、それぞれのIC50は27 nM、135 nM、120 nMです。FGFR1、FLT3、LCK、PLK1、STLK2、VEGFR2/3に対するIC50は10～200倍高いです。
in vitro PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. This compound 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. It 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. This chemical (0.5 μM) causes polyploidy in tumor cells. The mechanism of action of this compound is in agreement with inhibition of Aurora kinases. This compound in association with radiation leads to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of this chemical (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.
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. This compound (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.

プロトコル(参考用のみ)

キナーゼアッセイ 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 this compound toward Aurora kinases is evaluated and IC50 values are determined.
細胞アッセイ 細胞株 HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells
濃度 0.001-1 μM, dissolved in DMSO as 10 mM stock solution
反応時間 72 hours
実験の流れ 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 control.
動物実験 動物モデル Mice (female athymic nude) xenografts models of p53−/− HCT116 cells
投薬量 40 mg/kg
投与方法 Intraperitoneal (i.p.) injection twice a day

参考

  • https://pubmed.ncbi.nlm.nih.gov/16818708/
  • https://pubmed.ncbi.nlm.nih.gov/18026198/

カスタマーフィードバック

Data from [Data independently produced by Cancer Res, 2013, 73(10), 3168-80]

Data independently produced by , , Dr. Zhang of Tianjin Medical University

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：

Primary cilia suppress the fibrotic activity of atrial fibroblasts from patients with atrial fibrillation in vitro [ Sci Rep, 2024, 14(1):12470] PubMed: 38816374
Aurora kinase A regulates cancer-associated RNA aberrant splicing in breast cancer [ Heliyon, 2023, 9(7):e17386] PubMed: 37415951
Nuclear Aurora kinase A switches m6A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4 [ Signal Transduct Target Ther, 2022, 7(1):97] PubMed: 35361747
FOP Negatively Regulates Ciliogenesis and Promotes Cell Cycle Re-entry by Facilitating Primary Cilia Disassembly [ Front Cell Dev Biol, 2020, 8:590449] PubMed: 33304902
Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion. [ Mol Cancer Res, 2019, 17(1):20-29] PubMed: 30131447
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370] PubMed: 30702467
HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma. [ EMBO Rep, 2017, 18(2):334-343] PubMed: 28028031
Lineage specificity of primary cilia in the mouse embryo. [Bangs FK, et al. Nat Cell Biol, 2015, 17(2):113-22]
Lineage specificity of primary cilia in the mouse embryo. [ Nat Cell Biol, 2015, 17(2):113-22] PubMed: 25599390
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

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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