Volasertib

別名：BI 6727

製品コード：S2235 純度：99.78%

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.

CAS No. 755038-65-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 37000	国内在庫あり
5mg	JPY 29500	国内在庫あり
25mg	JPY 71500	国内在庫あり
100mg	JPY 145500	国内在庫あり
1g	JPY 295500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（161）

製品安全説明書

現在のバッチを見る：純度： 99.78%

99.78

Volasertib関連製品

関連ターゲット	PLK1 PLK2 PLK3 PLK4	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

PLKシグナル伝達経路

PLK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
DU145	Growth Inhibition Assay	10/50/250 nM	24 h	IC50<10 nM	23884428
T98G	Growth Inhibition Assay	50-150 nM	72 h	inhibits cell proliferation	23887645
SF188	Growth Inhibition Assay	50-150 nM	72 h	inhibits cell proliferation	23887645
FaDu	Growth Inhibition Assay	0-1000 nM	1-4 d	inhibits cell growth in both dose- and time-dependent manner	23891096
A431	Growth Inhibition Assay	0-30 nM	1-4 d	inhibits cell growth in both dose- and time-dependent manner	23891096
HCC1428/LTED	Growth Inhibition Assay	2.5-40 nM	5 d	inhibits cell growth in a dose-dependent manner	25480943
MCF7/LTED	Growth Inhibition Assay	2.5-40 nM	5 d	inhibits cell growth in a dose-dependent manner	25480943
LNCaP	Growth Inhibition Assay	10/50/250 nM	24 h	IC50<10 nM	23884428
PC3	Growth Inhibition Assay	10/50/250 nM	24 h	IC50∼600 nM	23884428
KMCH-1	Apoptosis Assay	200 nM	24 h	induces apoptosis	23703673
Mz-ChA-1	Apoptosis Assay	200 nM	24 h	induces apoptosis	23703673
HUCCT-1	Apoptosis Assay	200 nM	24 h	induces apoptosis	23703673
THP-1	Growth Inhibition Assay		72 h	IC50=56±39 nM	25576074
SKM-1	Growth Inhibition Assay		72 h	IC50=95±52 nM	25576074
OCI-AML3	Growth Inhibition Assay		72 h	IC50=90±51 nM	25576074
NOMO-1	Growth Inhibition Assay		72 h	IC50=145±7 nM	25576074
MV-4-11	Growth Inhibition Assay		72 h	IC50=16±6 nM	25576074
MOLM-13	Growth Inhibition Assay		72 h	IC50=57±44 nM	25576074
KG-1	Growth Inhibition Assay		72 h	IC50=150±67 nM	25576074
KASUMI-1	Growth Inhibition Assay		72 h	IC50=170±51 nM	25576074
RT4	Growth Inhibition Assay		48 h	IC50=111.27 nM	23792639
5637	Growth Inhibition Assay		48 h	IC50=1165.14 nM	23792639
T24	Growth Inhibition Assay		48 h	IC50=204.91 nM	23792639
SKBR3	Cytotoxicity assay		24 hrs	Cytotoxicity against human SKBR3 cells after 24 hrs by MTT assay	29288948
MDA-MB-231	Cytotoxicity assay		24 hrs	Cytotoxicity against human MDA-MB-231 cells after 24 hrs by MTT assay	29288948
MDA-MB-468	Cytotoxicity assay		24 hrs	Cytotoxicity against human MDA-MB-468 cells after 24 hrs by MTT assay	29288948
BT474	Cytotoxicity assay		24 hrs	Cytotoxicity against human BT474 cells after 24 hrs by MTT assay	29288948
ZR-75-1	Cytotoxicity assay		24 hrs	Cytotoxicity against human ZR-75-1 cells after 24 hrs by MTT assay	29288948
HCT 116	Growth Inhibition Assay			EC50 = 23 nM	19383823
NCI-H460	Growth Inhibition Assay			EC50 = 21 nM	19383823
BRO	Growth Inhibition Assay			EC50 = 11 nM	19383823
GRANTA-519	Growth Inhibition Assay			EC50 = 15 nM	19383823
HL-60	Growth Inhibition Assay			EC50 = 32 nM	19383823
THP-1	Growth Inhibition Assay			EC50 = 36 nM	19383823
Raji	Growth Inhibition Assay			EC50 = 37 nM	19383823
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
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生物活性

製品説明

特性

A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.

Targets

PLK1 ^[1]
(Cell-free assay)

0.87 nM

In Vitro
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]
Kinase Assay	In vitro kinase assays
Kinase Assay	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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-PLK1 / PLK1 p-AKT / AKT / p-MAPK / MAPK PARP / c-myc p-c-Met / c-Met / p-FAK / FAK / p-Src / Src Fibronectin / β-integrin / p-vimentin / Vimentin / p-HH3		29108241
	Immunofluorescence	PLK1 / Wee1		29108241
	Growth inhibition assay	Cell viability		29383095

In Vivo
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]
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
	投与量	~25 mg/kg/day
	投与経路	Injected i.v., or given intragastrally via gavage needle

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT02722135	Withdrawn	Leukemia Myeloid Acute	Boehringer Ingelheim	November 2016	Phase 1
NCT02721875	Terminated	Myelodysplastic Syndromes	Boehringer Ingelheim	April 28 2016	Phase 1
NCT02201329	Completed	Myelodysplastic Syndromes\|Leukemia Myelomonocytic Chronic	Boehringer Ingelheim	August 2014	Phase 1
NCT01971476	Completed	Leukemia\|Neoplasms	Boehringer Ingelheim	October 22 2013	Phase 1
NCT01772563	Completed	Neoplasms	Boehringer Ingelheim	February 4 2013	Phase 1
NCT01662505	Completed	Leukemia Myeloid Acute	Boehringer Ingelheim	August 2012	Phase 1

参考
[1] Rudolph D, et al. Clin Cancer Res, 2009, 15(9), 3094-3102. [2] Grinshtein N, et al. Cancer Res, 2011, 71(4), 1385-1395. [3] Harris PS, et al. BMC Cancer, 2012, 12, 80.

参考

化学情報

分子量	618.81	化学式	C₃₄H₅₀N₈O₃
CAS No.	755038-65-4	SDF	Download Volasertib SDFをダウンロードする
Smiles	CCC1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 35 mg/mL ( (56.56 mM)； Warmed with 50℃ water bath; 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問1:
I wonder how to reconstitute the inhibitor for in vivo studies?

回答
Volasertib can be dissolved in 4% DMSO+Corn oil at 2mg/ml for i.p. injection in mice. For oral administration, it can be formulated in hydrochloric acid (0.1 N), and diluted with 0.9% NaCl, or suspended in 0.5% Natrosol 250 hydroxyethyl-cellulose as indicated in the publications. We also suggest the vehicle 30% PEG400/0.5% Tween80/5% propylene glycol for a suspension which we tested in house.

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