Linsitinib (OSI-906)

目录号:S1091

仅限科研使用

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。

Linsitinib (OSI-906) Chemical Structure

CAS: 867160-71-2

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 5899.91 现货
RMB 13677.3 现货
大包装 有超大折扣
大剂量询单有大折扣!

今日订购,明日送达 全国免运费 分装免费 分装成小规格产品(单支最小为1mg)
如1支10mg产品可分装为10支1mg产品

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Linsitinib (OSI-906)发表文献159篇:

产品安全说明书

IGF-1R抑制剂选择性比较

相关IGF-1R产品

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 NVn1TJNDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXyTWM2OD1yLkCyPFA3KM7:TR?= MkDTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
KS-1 NGDLdpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrIbXFKUUN3ME2wMlA{QDN3IN88US=> M2nNb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExQTF4NESvK|5USU6JRWK8M4E,
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EW-1 NULB[IxmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTBwMEi1PFUh|ryP M{niXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExQTF4NESvK|5USU6JRWK8M4E,
HMV-II NIXvW29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPmPItKSzVyPUCuNFg5PDZizszN M13sflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExQTF4NESvK|5USU6JRWK8M4E,
COLO-205 MkTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnCcVVKSzVyPUCuNVA1PTRizszN NHX6[pE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODlzNkS0M{c,W0GQR1XSQE9iRg>?
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HT-144 NHPPZ2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonhTWM2OD1yLkK2NVkyKM7:TR?= NHzD[3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODlzNkS0M{c,W0GQR1XSQE9iRg>?
LAN-6 M3ztTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTBwMk[zOFgh|ryP MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFkyPjR2Lze+V2FPT0WUPD;hQi=>
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SNU-C1 NGfNRoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUK3ZVBEUUN3ME2wMlI6OzF|IN88US=> MlzCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA6OTZ2ND:nQnNCVkeHUkyvZV4>
RS4-11 NUPVU5lET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknZTWM2OD1yLkOzO|U5KM7:TR?= M2\RTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExQTF4NESvK|5USU6JRWK8M4E,
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RT-112 MoLrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPSXYZKSzVyPUiuNFk3PzdizszN NH;ZcY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODlzNkS0M{c,W0GQR1XSQE9iRg>?
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HCC1187 MoH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPyUJJuUUN3ME24MlI6OzlzIN88US=> NE\xW4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODlzNkS0M{c,W0GQR1XSQE9iRg>?
NCI-H2030 MoXLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHO5[nJKSzVyPUiuN|c4OTRizszN NFfyR|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODlzNkS0M{c,W0GQR1XSQE9iRg>?
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Assay
Methods Test Index PMID
Western blot p-EGFR / EGFR / p-IGF1R / IGF1R / p-IRS1 / IRS1 / p-ERK / ERK / p-AKT / AKT p-IGF1R / IGF1R / p-mTOR / mTOR cleaved caspase-3 / cleaved PARP pSrc(Y416) / Src p-STAT3(Y705) / STAT3 pS6 / S6 26052929 28440057 26515601 26041671 21257723
Immunofluorescence FoxO1 27535223
Growth inhibition assay Cell 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]
  • 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]
  • 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。
动物实验:[1]
  • 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

溶解度(25°C)

体外

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 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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)

mg/kg g μL

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
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

摩尔浓度计算器

质量 浓度 体积 分子量

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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.