PHA-680632

製品コードS1454 バッチS145401

化学情報

	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)
		Ethanol	100 mg/mL (199.35 mM)
		Water	Insoluble
* <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 is a potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3.
in vitro	PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. PHA-680632 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. PHA-680632 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. PHA-680632 (0.5 μM) causes polyploidy in tumor cells. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. ^[1] PHA680632 in association with radiation leads 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 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. ^[2]
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. PHA-680632 (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. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Aurora Kinase Inhibition Assay
キナーゼアッセイ	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 the 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 cont
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

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：

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
Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide. [He Q, et al Mol Biol Cell, 2014, 25(11):1715-29]	PubMed: 24694597

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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