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BMS-754807

现货
Catalog No.
A1185
有效的、选择性的IGF-1R和InsR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 900.00
现货
5mg
¥ 650.00
现货
25mg
¥ 2,500.00
现货
100mg
¥ 7,000.00
现货

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Background

BMS-754807 is a potent and small molecular inhibitor which targets the IGF-1R/IR family kinases with Ki <2 nmol/L[1]. The efficacy of BMS-754807 on normal tissues and tumor cell cycle is believed to be different from the effects of continuous inhibition by anti-IGF-1R antibodies.[2]

BMS-754807 could effectively inhibit the growth of many human tumor types from in vitro perspective, such as mesenchymal, hematopoietic and epithelial tumor cell lines with an IC50 value of 5–365 nmol/L. It can also induce sub-G1 fraction accumulation and an increase in poly ADP ribose polymerase and Caspase 3 cleavage, suggesting that it can lead to apoptosis in a human rhabdomyosarcoma cell line (Rh41). Furthermore, as a pyrrolotriazine and reversible ATP-competitive antagonist of IGF-1R, BMS-754807 was shown to inhibit the catalytic domain of the IGF-1R, and proved to inhibit the IGF-1R and IR activity by using the in-vitro kinase assays. Since the antibodies can bind to IGF-1R but not to IR, this could be regardere as an escape mechanism for IGF-II and insulin signaling.[3]

References:
[1] Q.S. Chu,S.W. Kim,P.M. Ellis,L. Mileshkin,R.H. de Boer,J.S. Park,T. Pellas,F. Huang,F. Graf Finckenstein,A. Dhar. BMS-754807, an oral dual IGF-1R/insulin receptor (IR) inhibitor: initial results from a Phase 1 dose- and schedule-finding study in combination with carboplatin/paclitaxel in subjects with solid tumors. European Journal of Cancer Supplements. November 2010, 8(7): 131.
[2] Vattoly J. Majo, Victoria Arango, Norman R. Simpson, Jaya Prabhakaran, Suham A. Kassir, Mark D. Underwood, Mihran Bakalian, Peter Canoll, J. John Mann, J.S. Dileep Kumar. Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R. Bioorganic & Medicinal Chemistry Letters. July 2013, 23(14): 4191-4194.
[3] Joan M. Carboni, Mark Wittman, Zheng Yang, et al.. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009;8:3341-3349.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt461.49
Cas No.1001350-96-4
FormulaC23H24FN9O
Solubility≥23.05mg/mL in DMSO
Chemical Name(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide
SDFDownload SDF
Canonical SMILESCC1(CCCN1C2=NN3C=CC=C3C(=N2)NC4=NNC(=C4)C5CC5)C(=O)NC6=CN=C(C=C6)F
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。

试验操作

细胞实验[1]:

细胞系

IGF-1R-Sal、Rh41和Geo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,细胞增殖抑制:72 h;磷酸化抑制:1 h

应用

用0.1-1000 nM的BMS-754807处理细胞后,通过3 H-胸苷掺入DNA来评估细胞增殖。在IGF-1R-Sal、Rh41和Geo细胞中,BMS-754807抑制细胞增殖,IC50分别为7、5和365 nM。BMS-754807抑制pIGF-1R的IC50值与其抑制下游成分(e.g., pAkt)的IC50值非常接近。与Rh41和Geo细胞相比,BMS-754807在IGF-1R-Sal细胞中更大程度地抑制pMAPK,表明在Rh41和Geo细胞中存在额外的补偿性通路(比如EGFR),其在驱动信号中可能具有重要作用。

动物实验[1]:

动物模型

各种肿瘤异种移植(Sal-IGF、GEO、Colo205、JJN3、Rh41或RD1)裸鼠

剂量

0.01 ml/g;口服给药

应用

在选定的上皮(IGF-1R-Sal、GEO和Colo205)、造血(JJN3)和间质(RD1和Rh41)异种移植肿瘤模型中,BMS-754807抑制肿瘤生长,TGI范围介于53%-115%之间。在高敏感性的Rh41横纹肌肉瘤中,BMS-754807以3.125 mg/kg的剂量每天两次和6.25 mg/kg的剂量每天一次给药均可有效抑制肿瘤生长。

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] Carboni J M, Wittman M, Yang Z, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Molecular Cancer Therapeutics, 2009, 8(12): 3341-3349.

生物活性

描述 MS-754807是一种有效的和选择性的IGF-1R和InsR抑制剂,IC50分别为1.8 nM和1.7 nM。
靶点 IGF-1R InsR        
IC50 1.8 nM 1.7 nM        

质量控制

化学结构

BMS-754807