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BI 2536ATP竞争性的Plk1抑制剂

BI 2536

产品编号:A3965
ApexBio 的所有产品仅用作科研,我们不为任何个人用途提供产品和服务
规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥1,250.00 10-15 工作日发货
5mg ¥850.00 10-15 工作日发货
10mg ¥1,500.00 10-15 工作日发货
50mg ¥4,700.00 10-15 工作日发货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1. Chen LL, Wang YB, et al. "Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2K2 and PLK1 in neuronal autophagy." Autophagy. 2017;13(11):1969-1980. PMID:28933595

质量控制

化学结构

BI 2536

相关生物数据

BI 2536

相关生物数据

BI 2536

BI 2536 Dilution Calculator

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BI 2536 Molarity Calculator

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化学性质

CAS号 755038-02-9 SDF Download SDF
别名 BI-2536;BI2536
化学名 4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide
SMILES CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C
分子式 C28H39N7O3 分子量 521.67
溶解度 ≥13.04 mg/mL in DMSO, ≥92.4 mg/mL in EtOH with ultrasonic, <2.56 mg/mL in H2O 储存条件 Store at -20°C
物理性状 A solid 运输条件 试用装:蓝冰运输。
其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议 为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

生物活性

描述 BI2536是一个有效的Plk1抑制剂,IC50值为0.83 nM。
靶点 Plk1          
IC50 0.83 nM          

实验操作

细胞实验[1]:

细胞系

HeLa-S3细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

1 μM;24 h

应用

BI 2536对癌细胞生长细胞周期的效应通过免疫荧光显微镜和流式细胞仪进行评估。BI2536引起HeLa细胞积累4N DNA含量,表明细胞周期阻滞在G2期或有丝分裂期。在BI 2536处理的培养HeLa细胞中,有丝分裂图片显示异常的有丝分裂,其EC50值与诱导G2/M期停滞的值非常接近。

动物实验[1]:

动物模型

植入HCT 116细胞的免疫缺陷nu/nu小鼠

剂量

40–50mg/kg,1或2次/周;静脉注射

应用

据报道,在不同的异种移植模型中,BI 2536具有很好的疗效。例如,在HCT 116结肠癌中,BI 2536每周2次给药显示完全肿瘤抑制,每周1次给药时T/C值为16%。在更严格的具有较大HCT 116肿瘤模型中,直到癌结节的中值达到500 mm3时才开始治疗,BI 2536五个周期的治疗诱导显著的肿瘤消退,而对照小鼠显示疾病的发展。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Steegmaier M, Hoffmann M, Baum A, et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Current Biology, 2007, 17(4): 316-322.

研究更新

1. Human ABCB1 (P-glycoprotein) and ABCG2 mediate resistance to BI 2536, a potent and selective inhibitor of Polo-like kinase 1. Biochem Pharmacol. 2013 Oct 1;86(7):904-13. doi: 10.1016/j.bcp.2013.08.004. Epub 2013 Aug 17.
Abstract
BI 2536, a Plk1 inhibitor, exhibits antiproliferative activity against cancer cells through promoting G2/M cell cycle arrest. Acquired BI 2536 resistance in ABCB1 or ABCB2 overexpressing human cancer cells is caused by BI 2536 induced inhibition of drug substrate transport mediated by ABC transporters and can be diminished by addition of inhibitors of ABC transporters.
2. A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer. Clin Lung Cancer. 2013 Jan;14(1):19-27. doi: 10.1016/j.cllc.2012.04.003. Epub 2012 Jun 1.
Abstract
The combination of BI 2536, a PlK1 inhibitor, and pemetrexed was evaluated for MTD, safety, efficacy and PK in previously treated advanced or metastatic non-small-cell lung cancer.
3. A randomized, open-label, phase I/II trial to investigate the maximum tolerated dose of the Polo-like kinase inhibitor BI 2536 in elderly patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2013 Oct;163(2):214-22. doi: 10.1111/bjh.12518. Epub 2013 Aug 16.
Abstract
BI 2536, a Plk inhibitor capable of inducing mitotic arrest and apoptosis, showed modest clinical activity (9% response rate) in elderly patients with relapsed/refractory AML, which increased bone marrow cells in G2/M with a characteristic pattern of mitotic catastrophe and caused haematological side effects.
4. PLK1 expression and BI 2536 effects in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014 Feb 12. doi: 10.1002/pbc.24978. [Epub ahead of print]
Abstract
PLK1, a mitotic events mediating kinase, is associated with poorly prognosed neoplasia and has not been assessed for its role in childhood ALL.
5. Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels. Neoplasia. 2012 May;14(5):410-9.
Abstract
BI 2536, a Plk1 inhibitor, reduced HCC cell viability, inhibited HCC xenograft progression in nude mice and diminished hepatocarcinogenesis in TGF α/c-myc bitransgenic mice. However, BI 2536 hardly affect HCC progression in the transgenic mouse HCC model due to resistance caused by low intratumoral levels of BI 2536.

产品描述

BI 2536是一个有效的、ATP竞争性的、耐受性良好、高特异性的人polo样激酶1(PLK1)抑制剂,IC50值为0.83 nM,比对其它激酶的作用强1000倍[1]。

据报道,BI2536可以抑制细胞生长和集落形成。在人宫颈癌细胞系HeLa中,BI2536诱导细胞周期停滞在G2 / M期,诱导细胞凋亡[2]。在超过20个的肿瘤细胞系中,BI 2536抑制细胞增殖,半数最大有效浓度(EC 50)的范围为2-25 nM。多个研究表明,在人癌异种移植模型中,BI2536以静脉注射的方式一周给药1-2次具有抗肿瘤活性[1]。

参考文献:
[1] Sch?ffski P.  Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
[2] Pezuk JA1, Brassesco MS, Oliveira JC, Morales AG, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG.  Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells. Clin Exp Med. 2013 Feb;13(1):75-80.