Linsitinib (OSI-906)

For research use only. Not for use in humans.

目录号:S1091

Linsitinib (OSI-906) Chemical Structure

CAS No. 867160-71-2

Linsitinib (OSI-906)是一种选择性IGF-1R抑制剂,在无细胞试验中IC50为35 nM;对InsR抑制作用适中,IC50为75 nM,对Abl,ALK,BTK,EGFR, FGFR1/2,PKA等没有抑制活性。Phase 3。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1550.54 现货
RMB 1393.48 现货
RMB 2226.24 现货
RMB 5899.91 现货
RMB 13677.3 现货
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客户使用Selleck生产的Linsitinib (OSI-906)发表文献147篇:

产品安全说明书

IGF-1R抑制剂选择性比较

生物活性

产品描述 Linsitinib (OSI-906)是一种选择性IGF-1R抑制剂,在无细胞试验中IC50为35 nM;对InsR抑制作用适中,IC50为75 nM,对Abl,ALK,BTK,EGFR, FGFR1/2,PKA等没有抑制活性。Phase 3。
靶点
IGF-1R [1]
(Cell-free assay)
Insulin Receptor [1]
(Cell-free assay)
IRR [1]
(Cell-free assay)
35 nM 75 nM 75 nM
体外研究

OSI-906 抑制IGF-IR自磷酸化和下游信号蛋白AKT, ERK1/2和S6激酶的激活,IC50为0.028到 0.13 μM。OSI-906通过与C-螺旋相互作用而使靶点蛋白形成中间结构形态。OSI-906作用于肝脏微粒体,具有良好的代谢稳定性。OSI-906浓度为1μM时,完全抑制IR 和IGF-IR磷酸化。OSI-906抑制一些肿瘤细胞系增殖,包括非小细胞肺癌和结肠直肠癌(CRC)肿瘤细胞系,EC50为0.021到 0.810 μM。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A4-Fuk M3PhNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zLWmlEPTB;MD6wNlgxPiEQvF2= MoXDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
KS-1 MmfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTROnVxUUN3ME2wMlA{QDN3IN88US=> NVj0WmRnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB7MU[0OE8oRlODTlfFVlww[T5?
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EW-1 MmKxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\ZTWM2OD1yLkC4OVg2KM7:TR?= NWf3Uo9[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB7MU[0OE8oRlODTlfFVlww[T5?
HMV-II MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mki1TWM2OD1yLkC4PFQ3KM7:TR?= NUXjNIpXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB7MU[0OE8oRlODTlfFVlww[T5?
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HT-144 NF7NT|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnq2TWM2OD1yLkK2NVkyKM7:TR?= MoGyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
LAN-6 M1vVRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoHjTWM2OD1yLkK2N|Q5KM7:TR?= Mk\5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
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RT-112 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPPNG5tUUN3ME24MlA6Pjd5IN88US=> Mnn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
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NCCIT MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\OTWM2OD17LkWzNVY6KM7:TR?= MkCxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-EGFR / EGFR / p-IGF1R / IGF1R / p-IRS1 / IRS1 / p-ERK / ERK / p-AKT / AKT; 

PubMed: 26052929     


Effects of linsitinib on EGFR and IGF1R Signaling Pathways. H1975, AR1, AR2 and AR3 cells were treated with control DMSO or linsitinib (2 and 5 μM) for 24 hours. Cell lysates were subjected to Western blot analysis. IGF1R-IRS-1-AKT phosphorylation was effectively inhibited by linsitinib in afatinib resistance cells whereas IRS-1-AKT phosphorylation was up-regulated by linsitinib in H1975 parental cells.

p-IGF1R / IGF1R / p-mTOR / mTOR ; 

PubMed: 28440057     


Linsitinib inhibits the activation of ERK and PI3K pathways. After treatment of Linsitinib at 0.1 or 1.0 μmol/L for 72 h, the phosphorylation of insulin‐like growth factor‐1 receptor (IGF‐1R), ERK1/2, and AKT/mTOR pathways were analyzed in TE‐13, TE‐1, and KYSE‐510 cell lines by western blot.

cleaved caspase-3 / cleaved PARP; 

PubMed: 28440057     


Reduced apoptosis in Linsitinib-resistant esophageal squamous cell carcinoma cells. After treatment of Linsitinib at 0.1 or 1.0 μmol/L for 72 h, cleaved PARP and activated Caspase‐3 were examined in TE-13, TE-1, and KYSE-510 cells by western blot. Tubulin was used as a loading control.

pSrc(Y416) / Src; 

PubMed: 26515601     


A549, H226Br, and H1975 cells were treated with 1 or 2 μM linsitinib (diluted in RPMI 1640 medium containing 10% FBS) for 12 or 24 h. Before harvest, cells were further stimulated with 10% FBS for 20 min. Cells were lysed with modified RIPA buffer and the protein expression was determined by Western blot analysis.

p-STAT3(Y705) / STAT3 ; 

PubMed: 26041671     


H226B and H460 cells were subject to daily treatment with linsitinib (1 μM) for 1-5 days.

pS6 / S6; 

PubMed: 21257723     


Western blot of NCI-H292 cells following 30 minutes of exposure to OSI-906 shows target inhibition of pIGF-1R and pIR at all doses as well as inhibition of downstream targets pAKT and pS6.

26052929 28440057 26515601 26041671 21257723
Immunofluorescence
FoxO1; 

PubMed: 27535223     


After starvation, control or βIRKO β-cell lines were treated with insulin (10 nm) in combination with high glucose (450 mg/dL), in the presence or absence of PI3K inhibitor LY294002, insulin receptor, and IGF1 receptor dual inhibitor OSI-906, Akt inhibitor MK2206, or MEK1/2 inhibitor U0126 for 30 min.  A, representative pictures of β-cells immunostained for FoxO1 (red) and DAPI (blue). The scale bar indicates 20 μm.

27535223
Growth inhibition assay
Cell viability; 

PubMed: 26136493     


InsR/IGF1R dual inhibitors, OSI-906 and BMS-754807, dose-dependently inhibited T4105 viability.

26136493
体内研究 OSI-906 作用于IGF-IR驱动的移植瘤鼠模型,抑制肿瘤生长,按 75 mg / kg剂量处理,导致100% TGI和 55% 衰退,按25 mg/kg剂量处理,导致 60% TGI,没有衰退。OSI-906处理犬,大鼠和小鼠,诱导不同的消除半衰期,消除半衰期分别为1.18 小时, 2.64小时 和2.14小时。OSI-906按不同剂量单独处理给药雌性Sprague-Dawley 大鼠和雌性CD-1小鼠,每天一次,Vmax值与OSI-906 剂量不成比例。OSI-906 按 25 mg/kg剂量处理12天,提高血糖值。OSI-906按75 mg/kg 剂量单独处理IGF-IR-驱动的人全长人类IGF-IR (LISN)移植鼠模型,在4 和24小时间最大程度抑制IGF-IR磷酸化(80%),血浆药物浓度为26.6-4.77 μM。[1] OSI-906 按60 mg/kg剂量单独作用于NCI-H292 移植鼠,处理2,4,24小时,抑制糖吸收。OSI-906 作用于NCI-H292移植鼠模型,抑制肿瘤生长。[2]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

蛋白激酶生化实验:

通过以ELISA为基础的检测法(IGF-IR, IR, EGFR 和 KDR)或使用100 µM ATP的放射检测法进行蛋白激酶检测实验。在内部ELISA检测实验中,使用聚 (Glu:Tyr)作为底物,结合到96孔实验板表面,使用辣根过氧化物酶标记的自磷酸化抗体测定磷酸化。使用ABTS作为过氧化物酶底物,通过在405/490 nm处测量吸光度而测定结合的抗体。所有实验使用纯化的重组激酶催化域。在昆虫细胞中,人类IGF-IR或EGFR的重组酶表达作为NH2-末端谷胱甘肽S-转移酶融合蛋白,且在内部纯化。通过抑制百分数对log10药品浓度的S型剂量-反应曲线测定IC50值。进行内部实验需重复进行实验,除非另有说明,取三次测量的最小值。
细胞实验:[1]
- 合并
  • Cell lines: MCF7, NCI-H292, Colo-205, HT29, H358, H1703, BxPC3, A673, SW620, DU4475, HepG2 和Hepa-1, RKO 3T3/hulGF-IR, H292 细胞
  • Concentrations: 0.02-0.8 μM
  • Incubation Time: 3天
  • Method: 为了测定细胞增殖,细胞接种在含FCS 10%的合适培养基上,在不同浓度OSI-906存在时,温育3天。通过细胞内ATP含量的荧光量化,使用CellTiterGlo测定抑制细胞生长的情况。数据作为衡量最大增殖的一部分,通过在不同浓度 OSI-906存在时的细胞密度除以对照组(只用DMSO处理)细胞密度。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: IGF-IR驱动的全长人类IGF-IR (LISN) 移植小鼠模型
  • Dosages: 25 mg/kg和75 mg/kg
  • Administration: 口服处理,每天一次,持续14天
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 84 mg/mL (199.29 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O
6.25mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 421.49
化学式

C26H23N5O

CAS号 867160-71-2
储存条件 粉状
溶于溶剂
别名 N/A

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 ul 动物数量
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
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • 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):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02546544 Completed Drug: Linsitinib Relapsed Ewing Sarcoma|Refractory Ewing Sarcoma University of Oxford|European Organisation for Research and Treatment of Cancer - EORTC|European Commission|Astellas Pharma Inc|Oxford University Hospitals NHS Trust March 2014 Phase 2
NCT01672736 Terminated Drug: ASP7487 Velcade Dexamethasone Multiple Myeloma University Health Network Toronto|Multiple Myeloma Research Consortium|Astellas Pharma Inc September 2012 Phase 1|Phase 2
NCT01529684 Completed Drug: radio-labeled OSI-906|Drug: OSI-906 Advanced Solid Tumors|Pharmacokinetics of 14C-OSI-906 Astellas Pharma Global Development Inc.|Astellas Pharma Inc March 19 2012 Phase 1
NCT01221077 Completed Drug: OSI-906|Drug: Erlotinib|Drug: Placebo NSCLC|Non Small Cell Lung Cancer Astellas Pharma Inc April 8 2011 Phase 2

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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:

    Does the inhibitor dissolve in the vehicle (30% PEG400/0.5%Tween 80/5% propylene glycol) or is it a suspension?

  • 回答:

    OSI-906 in 30% PEG400/0.5%Tween 80/5% propylene glycol is a suspension.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID