Sonidegib (NVP-LDE225)

目录号:S2151 别名: Erismodegib

Sonidegib (NVP-LDE225) Chemical Structure

Molecular Weight(MW): 485.5

Sonidegib (Erismodegib, NVP-LDE225)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。

规格 价格 库存 购买数量  
In DMSO RMB 1727.35 现货
RMB 1219.02 现货
RMB 2235.15 现货
RMB 3844.77 现货
RMB 5731.59 现货
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客户使用Selleck该产品发表文献27篇:

产品安全说明书

Hedgehog/Smoothened抑制剂选择性比较

生物活性

产品描述 Sonidegib (Erismodegib, NVP-LDE225)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
Smo (mouse) [1]
(Cell-free assay)
Smo (human) [1]
(Cell-free assay)
1.3 nM 2.5 nM
体外研究

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780ip2 MUjDfZRwgGmlaYT5JIF{e2G7 M4j0NZ4yOCEQvF2= MVHJR|UxRTF{IN88US=> M3nre|IzPTV|M{W1
A2780cp20 MV;DfZRwgGmlaYT5JIF{e2G7 NYjEOGVLhjFyIN88US=> MlXhTWM2OD15LkWg{txO MknwNlI2PTN|NUW=
SKOV3ip1 MWDDfZRwgGmlaYT5JIF{e2G7 NYi4S3M5hjFyIN88US=> NGXoSpVKSzVyPUK0JO69VQ>? MljTNlI2PTN|NUW=
SKOV3TRip2 NWj2So8{S3m2b4jpZ4l1gSCjc4PhfS=> NVvSZo9PhjFyIN88US=> NH75T2dKSzVyPUGyJO69VQ>? NHy2VowzOjV3M{O1OS=>
HeyA8 NW\3WHFuS3m2b4jpZ4l1gSCjc4PhfS=> MoDLglExKM7:TR?= M1r2NWlEPTB;MUig{txO MU[yNlU2OzN3NR?=
HeyA8MDR M1vQTmN6fG:6aXPpeJkh[XO|YYm= MYf+NVAh|ryP MVTJR|UxRThizszN NHjhN4szOjV3M{O1OS=>
OS5 NV3obYU6T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MUL+OUDPxE1? MWjy[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w M3XHclI{OjR|NUm1
OS18 M{LDU2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MlG3glUh|ryP MkLNdoVlfWOnczD0bIUheHKxbHnm[ZJifGmxbh?= MXKyN|I1OzV7NR?=
Glioblastoma initiating cells MV\DfZRwgGmlaYT5JIF{e2G7 NYTjZm16hjFyIN88US=> NFXEV5pKdmirYnn0d{BE\WyuIG\pZYJqdGm2eR?= NWnnc2xwOjN2OEK2O|E>
Glioblastoma initiating cells NHrBRZRHfW6ldHnvckBie3OjeR?= M3\3e54yOCEQvF2= NUL3SXd6cW6qaXLpeJMhdmW3cn;zdIhmemViZn;ycYF1cW:w MUOyN|Q5OjZ5MR?=
Glioblastoma initiating cells NEHlV|hEgXSxeHnjbZR6KGG|c3H5 NYnEcmEzhjFyIN88US=> NH7LemRqdmS3Y3XzJIFxd3C2b4Ppdy=> M4XsflI{PDh{Nkex
Glioblastoma initiating cells M{jXeGZ2dmO2aX;uJIF{e2G7 M3r5c54yOCEQvF2= MV;kc5dvemWpdXzheIV{KHSqZTDTTGghe2mpbnHsbY5oKHCjdHj3ZZk> NGHv[WwzOzR6Mk[3NS=>
Glioblastoma initiating cells NGLFPZhHfW6ldHnvckBie3OjeR?= Mlu3glExKM7:TR?= M3TJZ2lvcGmkaYTzJJRp\SCHeIDy[ZN{cW:wIH;mJGdmdmW|IFnueo9tfmWmIHnuJG1icW62YXnubY5oKFCudYLpdI91\W6leR?= M2myO|I{PDh{Nkex
Glioblastoma initiating cells MV\GeY5kfGmxbjDhd5NigQ>? MWr+NVAh|ryP NWPkWoNuUW6qaXLpeJMhVW:2aXzpeJktKEmwdnHzbY9vNCCjbnSgUYloemG2aX;u M4WwbFI{PDh{Nkex
LOX IMVI MnXkSpVv[3Srb36gZZN{[Xl? MoX0NVAh|ryP MWjEUXNQ M33oV4lvcGmkaYTzJGhm\GenaH;nMWdNUSCyYYToe4F6 MVKyN|k{PTl{NR?=
UACC 257 Mlz2SpVv[3Srb36gZZN{[Xl? MlH1NVAh|ryP MX\EUXNQ NFvFRpdqdmirYnn0d{BJ\WSpZXjv[{1IVElicHH0bJdigQ>? MV[yN|k{PTl{NR?=
LOX IMVI Mm\ZSpVv[3Srb36gZZN{[Xl? NHL0R4UyOCEQvF2= NUTJXmdDTE2VTx?= NX31NY9wcW6mdXPld{BIOSClZXzsJIN6[2ynIHHydoV{fA>? NUfQWYVKOjN7M{W5NlU>
UACC 257 MUDGeY5kfGmxbjDhd5NigQ>? M{[zXlExKM7:TR?= NIn0d2NFVVOR MVrpcoR2[2W|IFexJINmdGxiY4njcIUh[XK{ZYP0 M{[wXVI{QTN3OUK1
LOX IMVI NXLZfVN3S3m2b4jpZ4l1gSCjc4PhfS=> MX6xNEDPxE1? M2TXNGROW09? MmO5[IVkemWjc3XzJJR2dW:{IHPlcIwhfmmjYnnsbZR6 M3myblI{QTN3OUK1
UACC 257 NYTLPXI3S3m2b4jpZ4l1gSCjc4PhfS=> NXS0W2tNOTBizszN MlnISG1UVw>? MkS0[IVkemWjc3XzJJR2dW:{IHPlcIwhfmmjYnnsbZR6 M2P4[|I{QTN3OUK1
LOX IMVI MVTBdI9xfG:|aYOgZZN{[Xl? MYGxNEDPxE1? MkXOSG1UVw>? MnXjbY5lfWOnczDhdI9xfG:|aYO= MUCyN|k{PTl{NR?=
UACC 257 MULBdI9xfG:|aYOgZZN{[Xl? MYWxNEDPxE1? NFHjO5NFVVOR MYLpcoR2[2W|IHHwc5B1d3Orcx?= M3;T[VI{QTN3OUK1
ACHN NGnyPHBIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MoG1glUh|ryP MUjEUXNQ MXPJR|UxRTJvM,MAje69VQ>? NX7WUVhGOjVyOUO0PVE>
769-P MU\Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NYfnSnlKhjVizszN NVn4b2hyTE2VTx?= NVrSfHBnUUN3ME2yMVPjiIoQvF2= M4jmUVI2ODl|NEmx
786-O MmnsS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M2jtR542KM7:TR?= NXrNem5CTE2VTx?= NXPZcGltUUN3ME2yMVPjiIoQvF2= NX;3OXhsOjVyOUO0PVE>
786-O SuR MmnHS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MYH+OUDPxE1? M1zk[mROW09? NYKyRlEzUUN3ME2yMVPjiIoQvF2= NV;lWmVPOjVyOUO0PVE>
SP53 MUXGeY5kfGmxbjDhd5NigQ>? MVKzNEDPxE1? NIPZc|lFVVOR MUHpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= NGn5V4QzPjh6NU[wPC=>
SP53 MnrwSpVv[3Srb36gZZN{[Xl? NXTSZ2V2OzBizszN MVTEUXNQ NVjmTXdncW6qaXLpeJMhfGinIG\MRVQudWWmaXH0[YQhTkGNIIPp[45idGmwZzDwZZRpf2G7 MkHLNlY5QDV4MEi=
HS5 M1LTcmZ2dmO2aX;uJIF{e2G7 MXizNEDPxE1? NYfCVm93TE2VTx?= M2HrcYlvcGmkaYTzJINmdGxiYXTo[ZNqd25iYX7kJI1q\3KjdHnvci=> M1iwTFI3QDh3NkC4
HS27a NGfJS2VHfW6ldHnvckBie3OjeR?= MkHWN|Ah|ryP M3XvUmROW09? NHHkZ3FqdmirYnn0d{Bk\WyuIHHkbIV{cW:wIHHu[EBucWe{YYTpc44> NV;OfWVTOjZ6OEW2NFg>
SP53 MoPKR5l1d3irY3n0fUBie3OjeR?= MoPLN|Ah|ryP MlzjSG1UVw>? NEe3PIRqdmS3Y3XzJIF2fG:yaHHnfS=> NEXxc3AzPjh6NU[wPC=>
Jeko NH64eHhEgXSxeHnjbZR6KGG|c3H5 MmP3N|Ah|ryP MWfEUXNQ NETBc4hqdmS3Y3XzJIF2fG:yaHHnfS=> NV3Hdld{OjZ6OEW2NFg>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Bcl2 / c-myc / Cyclin D1 / pERK / ERK / pJNK / JNK / Caspase 3 / Cleaved caspase 3 ; 

PubMed: 22821765     


Immunoblot experiment of protein lysate from OPM1 cells treated with NVP-LDE225 (5μM) for 12, 24, and 36 hours and fractionated by electrophoresis and stained with different Abs as shown in figure (left). Cells were treated with different concentrations o䲧疝Ỵ疞㧀疜膉痘 瘿⟸෕ᾰƌ෕Ð 㺣痖帉痖Ѐ瑖堘𢡄빢᎒෕Ð鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸

Gli-1 / Gli-2 / p-Akt / Akt; 

PubMed: 25093491     


Western blot analysis on total cell lysates from renal cancer cell lines treated with NVP-LDE225 at different concentrations. Densitometric measurements were normalised to β-actin and reported under western blot images.

pp70S6K / P70s6k; 

PubMed: 25093491     


Percentage of survival of 786-O, 786-O SuR, and 769-P renal cancer cell lines treated with NVP-LDE225 and everolimus or their combination, as measured by the MTT assay. Data represent the mean (±s.d.) of three independent experiments, each performed in tr䲧疝Ỵ疞㧀疜膉痘 瘿뙠ෆᾰƌෆĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ෆĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ�෋䐺痖暼瘿�෋ᾰƌ �෋Ð㺣痖�෋€𢡄�෋€䀷痗�෋౴�෋㵶痗�෋뺖᎒泌Itemセ᎒Count﫨呂�෋猴፲�

p-p130CAS / p130CAS / p-FAK / FAK / p-Paxillin / Paxillin; 

PubMed: 25093491     


Western blot analysis of total cell lysates from 786-O, 786-O SuR, and 769-P human renal cancer cell lines treated with NVP-LDE225 (2.5 μm), everolimus (1 μm), and their combination. Densitometric measurements were normalised to β-actin and reported under䲧疝Ỵ疞㧀疜膉痘 

22821765 25093491
Immunofluorescence
GLI1; 

PubMed: 22821765     


U266 were cultured in the presence of control medium or NVP-LDE225 (5μM) for 24 hours. Immunocytochemical analysis was assessed using anti-Gli1 Ab, and 4,6-diamidino-2-phenylindole was used to stain nuclei. The cells were analyzed using an epifluorescence䲧疝Ỵ疞㧀疜膉痘 瘿⟸෕ᾰƌ෕Ð 㺣痖帉痖Ѐ瑖堘𢡄빢᎒෕Ð鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ뙠ෆ䐺痖暼瘿뙠ෆᾰƌ 뙠ෆÐ㺣痖뙠ෆ€𢡄뙤ෆ€

22821765
体内研究 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]

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)

细胞实验:

[1]

- 合并
  • Cell lines: TM3Hh12 细胞
  • Concentrations: 0 μM -10 μM
  • Incubation Time: 30 分钟
  • Method:

    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。


    (Only for Reference)
动物实验:

[1]

- 合并
  • 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
  • Formulation: 用0.5%纤维素钠配制
  • Dosages: 40 mg/kg/天
  • Administration: 口服,每天两次
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 97 mg/mL (199.79 mM)
Ethanol 97 mg/mL warmed (199.79 mM)
Water 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):
2% DMSO+corn oil
10mg/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 485.5
化学式

C26H26F3N3O3

CAS号 956697-53-3
储存条件 粉状
溶于溶剂
别名 Erismodegib

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、MSDS / 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、MSDS / 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
NCT02254551 Terminated Drug: LDE225|Drug: Bortezomib Multiple Myeloma SCRI Development Innovations LLC|Novartis January 2015 Phase 2
NCT02138929 Active not recruiting Drug: Everolimus|Drug: LDE 225 Esophageal Cancer M.D. Anderson Cancer Center|Novartis|National Cancer Institute (NCI) November 10 2014 Phase 1
NCT02195973 Completed Drug: LDE225 Recurrent Ovarian Cancer University of Alabama at Birmingham|Novartis Pharmaceuticals September 2014 Phase 1
NCT02027376 Completed Drug: LDE225|Drug: Docetaxel Advanced Breast Cancer Spanish Breast Cancer Research Group|Novartis May 2014 Phase 1
NCT02111187 Completed Drug: LDE225 Prostate Cancer Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins April 2014 Phase 1
NCT02086513 Terminated Drug: LDE225 Graft Versus Host Disease Massachusetts General Hospital|Novartis April 2014 Phase 1

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Hedgehog/Smoothened Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID