Sonidegib
别名: NVP-LDE225, Erismodegib 中文名称：索尼德吉
Sonidegib是一种Smoothened(Smo)拮抗剂，抑制Hedgehog (Hh)信号通路，无细胞试验中IC50分别为1.3 nM (小鼠)和2.5 nM(人)。Phase 3。
Sonidegib Chemical Structure
CAS: 956697-53-3
产品质控
批次：
纯度：
99.90%
99.90
Sonidegib相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| UACC 257 | Function assay | 10 μM | inhibits Hedgehog-GLI pathway | 23935925 | |
| LOX IMVI | Function assay | 10 μM | inhibits Hedgehog-GLI pathway | 23935925 | |
| Glioblastoma initiating cells | Function assay | ~10 μM | Inhibits Motility, Invasion, and Migration | 23482671 | |
| Glioblastoma initiating cells | Function assay | ~10 μM | Inhibits the Expression of Genes Involved in Maintaining Pluripotency | 23482671 | |
| Glioblastoma initiating cells | Function assay | ~10 μM | downregulates the SHH signaling pathway | 23482671 | |
| Glioblastoma initiating cells | Cytoxicity assay | ~10 μM | induces apoptosis | 23482671 | |
| Glioblastoma initiating cells | Function assay | ~10 μM | inhibits neurosphere formation | 23482671 | |
| Glioblastoma initiating cells | Cytoxicity assay | ~10 μM | Inhibits Cell Viability | 23482671 | |
| OS18 | Growth inhibitory assay | ~5 μM | reduces the proliferation | 23243595 | |
| OS5 | Growth inhibitory assay | ~5 μM | reduces the proliferation | 23243595 | |
| HeyA8MDR | Cytoxicity assay | ~10 μM | IC50=8 μM | 22553355 | |
| HeyA8 | Cytoxicity assay | ~10 μM | IC50=18 μM | 22553355 | |
| SKOV3TRip2 | Cytoxicity assay | ~10 μM | IC50=12 μM | 22553355 | |
| SKOV3ip1 | Cytoxicity assay | ~10 μM | IC50=24 μM | 22553355 | |
| A2780cp20 | Cytoxicity assay | ~10 μM | IC50=7.5 μM | 22553355 | |
| A2780ip2 | Cytoxicity assay | ~10 μM | IC50=12 μM | 22553355 | |
| LOX IMVI | Function assay | 10 μM | induces G1 cell cycle arrest | 23935925 | |
| UACC 257 | Function assay | 10 μM | induces G1 cell cycle arrest | 23935925 | |
| LOX IMVI | Cytoxicity assay | 10 μM | decreases tumor cell viability | 23935925 | |
| UACC 257 | Cytoxicity assay | 10 μM | decreases tumor cell viability | 23935925 | |
| LOX IMVI | Apoptosis assay | 10 μM | induces apoptosis | 23935925 | |
| UACC 257 | Apoptosis assay | 10 μM | induces apoptosis | 23935925 | |
| ACHN | Growth inhibitory assay | ~5 μM | IC50=2-3 μM | 25093491 | |
| 769-P | Growth inhibitory assay | ~5 μM | IC50=2-3 μM | 25093491 | |
| 786-O | Growth inhibitory assay | ~5 μM | IC50=2-3 μM | 25093491 | |
| 786-O SuR | Growth inhibitory assay | ~5 μM | IC50=2-3 μM | 25093491 | |
| SP53 | Function assay | 30 μM | inhibits cell adhesion and migration | 26885608 | |
| SP53 | Function assay | 30 μM | inhibits the VLA4-mediated FAK signaling pathway | 26885608 | |
| HS5 | Function assay | 30 μM | inhibits cell adhesion and migration | 26885608 | |
| HS27a | Function assay | 30 μM | inhibits cell adhesion and migration | 26885608 | |
| SP53 | Cytoxicity assay | 30 μM | induces autophagy | 26885608 | |
| Jeko | Cytoxicity assay | 30 μM | induces autophagy | 26885608 | |
| U2OS | Function assay | 2 hrs | Displacement of [3H]cyclopamine from wild type Smo expressed in U2OS cells after 2 hrs by scintillation counting, Ki = 0.006 μM. | 23063522 | |
| NIH/3T3 | Function assay | 24 hrs | Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells measured after 24 hrs by Gli-dual luciferase reporter gene assay, IC50 = 0.006 μM. | 27810591 | |
| TM3 | Function assay | 48 hrs | Inhibition of Hh signaling pathway in mouse TM3 cells assessed as downregulation of Gli1 gene expression after 48 hrs by luciferase reporter gene assay, EC50 = 0.0012 μM. | 26976215 | |
| NIH3T3 | Function assay | 48 hrs | Inhibition of SHH signaling pathway in mouse NIH3T3 cells measured after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0055 μM. | 24176396 | |
| NIH3T3 | Function assay | 48 hrs | Inhibition of Sonic-induced hedgehog signalling in mouse NIH3T3 cells after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0055 μM. | 26820554 | |
| NIH/3T3 | Function assay | Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells expressing wild type Smo assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0044 μM. | 27810591 | ||
| NIH/3T3 | Function assay | Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells harboring Smo D477H mutant assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0227 μM. | 27810591 | ||
| NIH/3T3 | Function assay | Inhibition of hedgehog signaling pathway expressed in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Gli-2 accumulation at tip of primary cilia by DAPI staining based confocal microscopic analysis | 27810591 | ||
| NIH/3T3 | Function assay | Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Smo-EGFP ciliary translocation by DAPI staining based confocal microscopic analysis | 27810591 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Sonidegib是一种Smoothened(Smo)拮抗剂，抑制Hedgehog (Hh)信号通路，无细胞试验中IC50分别为1.3 nM (小鼠)和2.5 nM(人)。Phase 3。 | ||||
|---|---|---|---|---|---|
| 特性 | LDE225 是具有高效性和选择性的使平滑的拮抗剂 | ||||
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | Sonidegib (Erismodegib, NVP-LDE225)可在0.6-0.8μM剂量上抑制1nM-25nM Hh激动剂Ag1.5 处理的TM3荧光报告细胞系。[1] | |||
|---|---|---|---|---|
| 细胞实验 | 细胞系 | TM3Hh12 细胞 | ||
| 浓度 | 0 μM -10 μM | |||
| 孵育时间 | 30 分钟 | |||
| 方法 | LDE225 用DMSO连续稀释后加入空的分析平板中。TM3Hh12 细胞 (TM3 细胞含有Hh的应答报告基因元件pTA-8xGli-Luc) 用含有5%的马血清，2.5%的胎牛血清(FBS)和15 mM HEPES, pH 7.3的F12 Ham’s/DMEM (1:1)培养基培养。收集细胞时用胰酶消化，然后用含有5%的马血清和15 mM HEPES, pH 7.3的F12 Ham’s/DMEM (1:1)培养基重悬，接着分铺到分析板中。然后加入LDE225在37 °C ，5% CO2的培养箱中大约孵育30分钟。接着加入1 nM 和25 nM 的Ag1.5到分析平板中，37 °C ，5% CO2的条件下培养。48小时后，向平板中加入Bright-Glo 或者 MTS试剂，测量492纳米下的荧光值或者吸收峰。通过MTS法检测Gli-驱动荧光素酶发光或吸光度信号，对浓度取Log（10）值做由非线性回归曲线，确定IC 50值。数据处理使用R统计软件包。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | Bcl2 / c-myc / Cyclin D1 / pERK / ERK / pJNK / JNK / Caspase 3 / Cleaved caspase 3 Gli-1 / Gli-2 / p-Akt / Akt pp70S6K / P70s6k p-p130CAS / p130CAS / p-FAK / FAK / p-Paxillin / Paxillin |
|
22821765 | |
| Immunofluorescence | GLI1 |
|
22821765 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | Sonidegib (Erismodegib, NVP-LDE225)与小鼠，大鼠以及人源的血浆蛋白有很强的结合能力(>99%)，同时与狗和猴子的血浆蛋白有适度的结合，结合能力分别是77 %和 85%。PAMPA 实验证明LDE225能够达到90.8%的渗透性。在梯度稀释的试验中，LDE225在临床物种上显示出很好的口服药效率，其生物药效率在69%到102%之间。LDE225呈弱碱性，pKa只有4.20，同时它的水溶性也相对较弱。LDE225被证明具有剂量依赖的抗肿瘤活性。给药剂量在5 mg/kg/天，一天一次时，LDE225明显抑制肿瘤生长，与33%的T/C值相一致。给药剂量在10 mg/kg/天，一天一次和 20 mg/kg/天，一天一次时，LDE225促使肿瘤退化的效果分别达到51%和83%。Gli1 mRNA抑制性与LDE225介导的肿瘤与血浆接触有关。在肿瘤移植的动物模型中，经过四天的给药处理，LDE225能够成功地穿过血脑屏障导致肿瘤生长受抑制[1]。LDE225能够使Rip1-Tag2小鼠中的肿瘤体积明显减少95.7%。LDE225减少LDE225给药处理小鼠的间质状标志基因的表达[2]。 | |
|---|---|---|
| 动物实验 | Animal Models | 采用无胸腺裸小鼠建立原位Ptch+/-p53-/-髓母细胞瘤同种异体移植模型 |
| Dosages | 40 mg/kg/天 | |
| Administration | 口服，每天两次 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02358161 | Completed | Pancreatic Cancer |
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Novartis|Celgene Corporation |
September 2015 | Phase 1|Phase 2 |
| NCT02254551 | Terminated | Multiple Myeloma |
SCRI Development Innovations LLC|Novartis |
January 2015 | Phase 2 |
| NCT02138929 | Completed | Esophageal Cancer |
M.D. Anderson Cancer Center|Novartis|National Cancer Institute (NCI) |
November 10 2014 | Phase 1 |
| NCT02195973 | Completed | Recurrent Ovarian Cancer |
University of Alabama at Birmingham|Novartis Pharmaceuticals |
September 2014 | Phase 1 |
| NCT02027376 | Completed | Advanced Breast Cancer |
Spanish Breast Cancer Research Group|Novartis |
May 2014 | Phase 1 |
| NCT02111187 | Completed | Prostate Cancer |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
April 2014 | Phase 1 |
化学信息&溶解度
| 分子量 | 485.5 | 分子式 | C26H26F3N3O3 |
| CAS号 | 956697-53-3 | SDF | Download Sonidegib SDF |
| Smiles | CC1CN(CC(O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F | ||
| 储存条件(自收到货起) | |||
|
体外溶解度 |
DMSO : 97 mg/mL ( (199.79 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 16 mg/mL (32.95 mM) Water : Insoluble |
摩尔浓度计算器 |
|
体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
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
只
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，注：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：取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：取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。
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