Linsitinib
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Linsitinib(OSI-906)是一种有效的和新型的小分子抑制剂,抑制胰岛素受体(IR)和胰岛素样生长因子1受体(IGF-1R)激酶,相应IC50值为75 nM和35 nM[1]。
3T3/hulGF-1R(LISN)细胞试验表明,Linsitinib抑制IGF-1R的配体依赖性自磷酸化及其下游信号传导通路,包括pERK1/2、pAKT和p-p70S6K的磷酸化。Linsitinib对多种癌细胞系具有抗增殖作用,包括结直肠癌细胞(SW620)、乳腺癌细胞(DY4475)以及小鼠成纤维细胞(3T3/hulGF-1R),相应EC50值为21 nM、86 nM和78 nM[1]。
在LISN异种移植模型中,口服给予Linsitinib可以呈剂量依赖性地抑制肿瘤生长[1]。
参考文献:
1. Mulvihill MJ1, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71
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Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 421.51 |
Cas No. | 867160-71-2 |
Formula | C26H23N5O |
Synonyms | OSI 906; OSI-906; OSI906 |
Solubility | ≥21.08 mg/mL in DMSO; insoluble in H2O; ≥2.88 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol |
SDF | Download SDF |
Canonical SMILES | CC1(CC(C1)C2=NC(=C3N2C=CN=C3N)C4=CC5=C(C=C4)C=CC(=N5)C6=CC=CC=C6)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验: [1] | |
细胞系 |
HepG2、Hep3B、Huh-7、PLC/PRF/5、SNU-387和SNU-423细胞 |
制备方法 |
该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
3 μM,20 hours |
实验结果 |
所有6个HCC细胞系中IR磷酸化程度比IGF-1R更高,表明IR活性在HCC中具有重要作用。此外,与OSI-906不敏感细胞系相比,对OSI-906敏感的3种HCC细胞系HepG2、Hep3B和HuH-7的IGF-1R和IR的磷酸化水平较高,这表明HCC细胞系中,细胞对OSI-906的敏感性与IGF-1R和IR的活化相关。 |
动物实验: [2] | |
动物模型 |
注射NCI-H292或NCI-H441细胞的雌性无胸腺裸鼠 |
给药剂量 |
口服,60 mg/kg |
实验结果 |
与载体处理的对照相比,对OSI-906治疗敏感的NCI-H292异种移植动物中,给予OSI-906后的第2、4和24小时18FDG摄取显著减少(p < 0.05)。对OSI-906治疗不敏感的NCI-H441异种移植动物在所评估的任何时间点18FDG摄取都未显示明显变化。NCI-H292异种移植物中,%ID/g下降,表明18FDG成像观察到的快速PD效应是通过OSI-906抑制IGF-1R和IR途径介导的。相比之下,对于NCI-H441异种移植物模型,载体对照和OSI-906治疗组之间的肿瘤样品中未观察到放射性示踪剂的摄取差异。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1] Zhao H, Desai V, Wang J, et al. Epithelial–Mesenchymal Transition Predicts Sensitivity to the Dual IGF-1R/IR Inhibitor OSI-906 in Hepatocellular Carcinoma Cell Lines. Molecular cancer therapeutics, 2012, 11(2): 503-513. [2] McKinley E T, Bugaj J E, Zhao P, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clinical Cancer Research, 2011, 17(10): 3332-3340. |
Description | OSI-906(Linsitinib)是IGF-1R的选择性抑制剂,其IC50值为35 nM;对InsR具有适度抑制作用,其IC50值为75 nM。 | |||||
靶点 | IGF-1R | InsR | ||||
IC50 | 35 nM | 75 nM |
质量控制和MSDS
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