Volasertib

别名: BI 6727

目录号：S2235 Purity: 99.78%

Volasertib是一种高度有效的Plk1抑制剂，无细胞试验中IC50为0.87 nM，比作用于Plk2和Plk3选择性高6和65倍。Volasertib可在多种癌细胞中诱导细胞周期停滞和自噬。Phase 3。

Volasertib Chemical Structure

CAS: 755038-65-4

规格	价格	库存
10mM (1mL in DMSO)	1654.53	现货
5mg	974.11	现货
25mg	3005.97	现货
100mg	7125.3	现货
1g	13677.3	现货
更大包装有超大折扣
400-668-6834 info@selleck.cn

产品质控

批次：纯度： 99.78%

99.78

Volasertib相关产品

相关靶点	PLK1 PLK2 PLK3 PLK4	点击展开
相关产品	BI 2536 Rigosertib (ON-01910) GSK461364 Onvansertib (NMS-P937) SBE 13 HCl Ro3280 CFI-400945 HMN-214 MLN0905 Poloxin	点击展开
相关化合物库	激酶抑制剂库 PI3K/Akt 抑制剂库 MAPK抑制剂库 DNA损伤/ DNA修复化合物库细胞周期化合物库	点击展开

细胞实验数据示例

细胞系	实验类型	给药浓度	孵育时间	活性描述	文献信息
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
点击查看更多细胞系数据

生物活性

产品描述

特性

BI6727具有高的体积分布，良好的组织穿透力和长的半衰期。

靶点

PLK1 ^[1]
(Cell-free assay)

0.87 nM

体外研究(In Vitro)
体外研究活性	如同BI2536，BI6727是属于dihydropteridinone类化合物的ATP竞争性激酶抑制剂。除了Plk1，BI6727也有效地抑制两个密切相关的激酶Plk2和Plk3，IC50分别为为5 nM和56 nM。 BI6727在浓度高达10 μM时对五十多种激酶均没有抑制活性。BI6727抑制从各种癌组织来源的多种细胞系的增殖，包括HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1 和 Raji 细胞，EC50 分别为23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM 和 37 nM。在NCI-H460细胞中，BI6727 (100 nM)诱导有丝分裂细胞聚集，这些细胞中有单极纺锤体和组蛋白H3的磷酸丝氨酸10阳性染色，这表明细胞处于M期，随后诱导细胞凋亡。^[1] BI6727低纳摩尔浓度表现对神经母细胞瘤（NB）肿瘤起始细胞（NB TIC）的抑制活性，EC 50为21 nM，而只有微摩尔浓度的BI6727对正常小儿神经干细胞有毒性作用。^[2] 类似于BI2536，BI6727诱导Daoy和ONS-76髓母细胞瘤细胞的生长停滞。^[3]
激酶实验	体外激酶抑制试验
激酶实验	重组人类Plk1的（残基1-603）是用杆状病毒表达系统表达的带有NH₂末端和GST-标记的融合采用的蛋白质。酶的活性测定法测定Plk1是在梯度稀释的BI6727中进行，以20 ng重组激酶以及10 μg牛乳酪蛋白为底物。激酶反应在60微升的终体积在30℃下进行45分钟[15 mM MgCl₂, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi γ-³²P-ATP]。反应通过加入125μL冰冷的5％三氯乙酸终止。转移沉淀到多屏幕混合酯纤维素过滤板后，洗涤板用1％三氯乙酸洗涤并测量辐射量。剂量-反应曲线用于计算IC 50值。
细胞实验	细胞系	HCT116，NCI-H460，BRO，GRANTA-519，HL-60，THP-1，和Raji细胞
	浓度	溶解在DMSO中至终浓度约1 μM
	孵育时间	24, 48和72小时
	方法	细胞增殖测定是将细胞孵育在不同浓度的BI6727中24，48和72小时，而后在荧光分光光度计上通过测量的Alamar蓝染料的转换测定。有效浓度在哪些细胞生长是由50％（EC 50）抑制从剂量 - 反应曲线拟合推断的。为了确定DNA含量，细胞悬浮液被固定在80％乙醇中，用含0.25％Triton X-100的PBS处理5分钟，并用含0.1％RNA酶和10 μg/mL的碘化丙锭的PBS室温孵育20分钟。细胞周期的测定是用流式细胞仪分析的。
实验图片	检测方法	检测指标	实验图片	PMID
	Western blot	Fibronectin / β-integrin / p-vimentin / Vimentin / p-HH3 p-c-Met / c-Met / p-FAK / FAK / p-Src / Src PARP / c-myc p-AKT / AKT / p-MAPK / MAPK p-PLK1 / PLK1		31040125
	Immunofluorescence	PLK1 / Wee1		29108241
	Growth inhibition assay	Cell viability		29383095

体内研究(In Vivo)
体内研究活性	BI6727显著抑制多种人类肿瘤异种移植物的生长，包括HCT116, NCI-H460, 和紫杉类耐药CXB1结肠癌，伴随着增加的有丝分裂指数以及细胞凋亡的增加。^[1] 体内研究表明，BI6727表现出比BI2536更好的毒性和药动学特征。^[3]
动物实验	Animal Models	雌性BomTac：NMRI-Foxn1^{NU小鼠腹腔移植HCT116，NCI-H460，或CXB1细胞。}
	Dosages	约25 mg/kg/day
	Administration	静脉注射，或通过灌胃针

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考文献
[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.

参考文献

化学信息&溶解度

分子量	618.81	分子式	C₃₄H₅₀N₈O₃
CAS号	755038-65-4	SDF	Download Volasertib SDF
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
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

DMSO : 35 mg/mL ( (56.56 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 30 mg/mL ( (48.48 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 20 mg/mL ( (32.32 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 20 mg/mL ( (32.32 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度
批次：

现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

动物体内配方计算器（澄清溶液）

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

计算结果：

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH₂O，混匀澄清。

体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。

注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

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操作手册

如果有其他问题，请给我们留言。

* 必填项

常见问题及建议解决方法

问题 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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Volasertib

产品质控

Volasertib相关产品

相关信号通路图

细胞实验数据示例

生物活性

化学信息&溶解度

实验计算

技术支持

常见问题及建议解决方法