产品说明书

Linsitinib

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Chemical Structure| 867160-71-2 同义名 : OSI-906
CAS号 : 867160-71-2
货号 : A139562
分子式 : C26H23N5O
纯度 : 99%+
分子量 : 421.494
MDL号 : MFCD12912153
存储条件:

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 50 mg/mL(118.63 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:

IP 2% DMSO+2% Tween80+40% PEG300+water 4 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点
  • IGF-1R

    IGF-1R, IC50:35 nM

  • Insulin Receptor

    Insulin Receptor, IC50:75 nM

描述 IGF-1R (insulin-like growth factor-1 receptor) plays a key role in transformation, growth and survival of malignant cells, and has been considered as a general and promising target for cancer treatment. Linsitinib is a potent and selective IGF-1R receptor with IC50 value of 35nM, also show inhibitory effect against Insulin receptor and insulin receptor-related receptor with IC50 values of 75nM for both (measured by purified recombinant kinase activity). Treatment with Linsitinib at concentration ranging in 0.01-1μM for 2h could dose-dependently inhibited autophosphorylation of IGF-1R, at phosphorylation of the downstream, including AKT, ERK and p70S6K with IC50 of 24nM, 130nM, 28nM and 60nM, respectively, in 3T3/huIGF-1R (LISN) cells. Also the inhibition on phosphorylation of both IGF-1R and IR by Linsitinib was shown in HT-29 and Colo-205 cells. The antiproliferative effect of Linsitinib could be observed in a panel of cell lines from various tumor types with IC50 ranging in 0.021-0.81μM, including HT29, Colo205, SW620 (colorectal), DU4475, MCF7 (breast), 3T3/huIGF-1R (mouse fibroblast), H358, H292 (non-small-cell lung), BxPC3 (pancreatic) and A673 (rhabdomyosarcoma) cell lines. A further study showed that a panel of non-small-cell lung cancer and colorectal cancer (CRC) tumor cell lines exhibiting an epithelial phenotype exhibited greater sensitivity to Linsitinib than those tumor cells that have undergone an epithelial–mesenchymal transition. A single oral dose of 75mg/kg Linsitinib inhibited the autophosphorylation of IGF-1R 2-24h after dose in LISN tumor xenograft models, suggesting the pharmacodynamics of this compound. Oral administration of Linsitinib at 75mg/kg once-daily for 12 days significantly inhibit tumor growth in a LISN xenograft model[1].
作用机制 Linsitinib can attach to the ATP-binding pocket of tyrosine kinase receptors, causing dual inhibition of both IR and IGF-1R.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22RV1 Growth Inhibition Assay IC50=5.80019 μM SANGER
5637 Growth Inhibition Assay IC50=13.7759 μM SANGER
639-V Growth Inhibition Assay IC50=27.0245 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.86mL

2.37mL

1.19mL

23.73mL

4.75mL

2.37mL

参考文献

[1]Murakami T, Singh AS, et al. Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. Oncotarget. 2016 Jul 26;7(30):47556-47564.