Volasertib

製品コードS2235 バッチS223508

化学情報

	Synonyms	BI 6727	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₃₄H₅₀N₈O₃
	分子量	618.81	CAS No.	755038-65-4
Solubility (25°C)*	体外	DMSO	35 mg/mL warmed with 50ºC water bath (56.56 mM)
		Water	Insoluble
		Ethanol	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	Volasertib is a highly potent Plk1 inhibitor with IC50 of 0.87 nM in a cell-free assay. It shows 6- and 65-fold greater selectivity against Plk2 and Plk3. Volasertib induces cell cycle arrest and apoptosis in various cancer cells. Phase 3.
in vitro	Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, BI6727 also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. BI6727 at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. BI6727 inhibits the proliferation of multiple cell lines derived from various cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells with EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively. BI6727 treatment (100 nM) in NCI-H460 cells induces an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, confirming that cells are arrested early in the M phase, followed by induction of apoptosis. ^[1] Low nanomolar concentrations of BI6727 display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of BI6727 are cytotoxic for normal pediatric neural stem cells. ^[2] BI6727 induces growth arrest of Daoy and ONS-76 medulloblastoma cells similar to BI 2536. ^[3]
in vivo	Administration of BI6727 significantly inhibits the growth of multiple human carcinoma xenografts including HCT116, NCI-H460, and taxane-resistant CXB1 colon carcinoma, accompanied by an increase in the mitotic index as well as an increase in apoptosis. ^[1] In in vivo studies, BI6727 shows better toxicity and pharmacokinetic profile compared to BI2536. ^[3]
特徴	A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase assays
キナーゼアッセイ	Recombinant human Plk1 (residues 1-603) is expressed as NH₂-terminal, GST-tagged fusion protein using a baculoviral expression system and purified by affinity chromatography using glutathione-agarose. Enzyme activity assays for Plk1 are done in the presence of serially diluted BI6727 using 20 ng of recombinant kinase and 10 μg casein from bovine milk as substrate. Kinase reactions are done in a final volume of 60 μL for 45 minutes at 30 °C [15 mM MgCl₂, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi γ-³²P-ATP]. Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transferring the precipitates to MultiScreen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curves are used for calculating IC50 value.
細胞アッセイ	細胞株	HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji
	濃度	Dissolved in DMSO, final concentrations ~1 μM
	反応時間	24, 48, and 72 hours
	実験の流れ	Cell proliferation assays are done by incubating cells in the presence of various concentrations of BI6727 for 24, 48, and 72 hours and cell growth is assessed by measuring Alamar blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth is inhibited by 50% (EC50) are extrapolated from the dose-response curve fit. To determine the DNA content, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide in PBS for 20 minutes at room temperature. Cell cycle profiles are determined by flow cytometric analysis.
動物実験	動物モデル	Female BomTac:NMRI-Foxn1^nu mice grafted s.c. with HCT116, NCI-H460, or CXB1 cells
	投薬量	~25 mg/kg/day
	投与方法	Injected i.v., or given intragastrally via gavage needle

参考

カスタマーフィードバック

: Data from [Oncogene, 2013, 10.1038/onc.2013.518]

: , , Dr. Xiangbing Meng from University of Iowa

: Data independently produced by , , Dr. Xiangbing Meng from University of Iowa

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：

PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti-tumor effects [ Mol Oncol, 2024, 10.1002/1878-0261.13610]	PubMed: 38361222
PLK1 phosphorylates RhoGDI1 and promotes cancer cell migration and invasion [ Cancer Cell Int, 2024, 24(1):73]	PubMed: 38355643
Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells [ Eur J Pharmacol, 2024, 963:176229]	PubMed: 38072041
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422]	PubMed: 37674080
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry [ Nat Commun, 2023, 14(1):355]	PubMed: 36683055
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505]	PubMed: 37845213
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8]	PubMed: 36736316
PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models [ J Clin Invest, 2023, 133(21)e162129]	PubMed: 37698938
PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models [ J Clin Invest, 2023, 133(21)e162129]	PubMed: 37698938
CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma [ Cell Death Differ, 2023, 30(8):1973-1987]	PubMed: 37468549

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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