Sonidegib (Erismodegib, NVP-LDE225)

製品コードS2151

Sonidegib (Erismodegib, NVP-LDE225)化学構造

分子量(MW):485.5

Sonidegib (Erismodegib, NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.

サイズ 価格(税別)  
JPY 34860.00
JPY 24900.00
JPY 44820.00
JPY 78020.00
JPY 116200.00

カスタマーフィードバック(3)

  • RU-SKI 43 blocks Shh signaling. (a) RU-SKI 43 blocks Gli activation. NIH 3T3 cells were cotransfected with vectors encoding 8× Gli-binding site (GliBS)-Firefly luciferase (unless indicated otherwise), Renilla luciferase reporter (pRL-TK) and Shh. Confluent cells were treated with DMSO, 10 μM LDE225, 10 μM RU-SKI 43 or 10 μM C-2. The firefly luciferase (FL)/Renilla luciferase (RL) ratio in cell lysates was calculated and normalized to that measured in DMSO-treated samples; error bars represent mean ± s.d. (n = 2–3). 

    Nat Chem Biol 2013 9, 247-9. Sonidegib (Erismodegib, NVP-LDE225) purchased from Selleck.

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

    Br J Cancer 2014 111(6), 1168-79. Sonidegib (Erismodegib, NVP-LDE225) purchased from Selleck.

  • NVP-LDE225, everolimus, sunitinib, and their combination interfere with actin and with intracellular organisation of focal adhesion points. Cytoskeleton organisation of 786-O SuR treated with NVP-LDE225 ( 2.5 uM ), everolimus (1 uM ), sunitinib (1 uM ), and their combination for 24 h was analysed by confocal microscopy. Actin-based structures were revealed by rhodaminated phalloidin staining (red fluorescence). Localisation of focal adhesion points was obtained by immunofluorescent staining of p-paxillin (green fluorescence). Merged row images show overlapping of p-paxillin and actin signals. Moreover, all captures were shown in transmitted light. Scale bars, 10 um.

    Br J Cancer 2014 111(6), 1168-79. Sonidegib (Erismodegib, NVP-LDE225) purchased from Selleck.

製品安全説明書

Hedgehog/Smoothened阻害剤の選択性比較

生物活性

製品説明 Sonidegib (Erismodegib, NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.
ターゲット
Smo (mouse) [1]
(Cell-free assay)
Smo (human) [1]
(Cell-free assay)
1.3 nM 2.5 nM
体外試験

Sonidegib (Erismodegib, NVP-LDE225) inhibits TM3 luciferized cell line with 0.6 nM and 8 nM, at the presence of 1 nM and 25 nM Hh agonist Ag1.5, respectively. [1]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780ip2 MoDYR5l1d3irY3n0fUBie3OjeR?= MmjEglExKM7:TR?= NHXlfXNKSzVyPUGyJO69VQ>? MkjJNlI2PTN|NUW=
A2780cp20 NVi3VVRYS3m2b4jpZ4l1gSCjc4PhfS=> MVP+NVAh|ryP MlO3TWM2OD15LkWg{txO NV7YS5ZTOjJ3NUOzOVU>
SKOV3ip1 NV;Ye5A4S3m2b4jpZ4l1gSCjc4PhfS=> MkTjglExKM7:TR?= MVPJR|UxRTJ2IN88US=> M4fKO|IzPTV|M{W1
SKOV3TRip2 MXvDfZRwgGmlaYT5JIF{e2G7 Mor2glExKM7:TR?= MXfJR|UxRTF{IN88US=> M2H1U|IzPTV|M{W1
HeyA8 M2jkbGN6fG:6aXPpeJkh[XO|YYm= MkHzglExKM7:TR?= NGHWVplKSzVyPUG4JO69VQ>? NU[3eJR6OjJ3NUOzOVU>
HeyA8MDR M{TQOWN6fG:6aXPpeJkh[XO|YYm= NH3EZ|R,OTBizszN M4npZ2lEPTB;ODFOwG0> MXqyNlU2OzN3NR?=
OS5 MlnlS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M3;aep42KM7:TR?= MUTy[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w MXeyN|I1OzV7NR?=
OS18 Mo\0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MlKwglUh|ryP NWXmbG13emWmdXPld{B1cGVicILvcIln\XKjdHnvci=> MVKyN|I1OzV7NR?=
Glioblastoma initiating cells MXPDfZRwgGmlaYT5JIF{e2G7 MV;+NVAh|ryP MlKzTY5pcWKrdIOgR4VtdCCYaXHibYxqfHl? MkSwNlM1QDJ4N{G=
Glioblastoma initiating cells M4DHT2Z2dmO2aX;uJIF{e2G7 NEnGbXd,OTBizszN M4[xZolvcGmkaYTzJI5mfXKxc4Do[ZJmKG[xcn3heIlwdg>? MnPaNlM1QDJ4N{G=
Glioblastoma initiating cells MkW4R5l1d3irY3n0fUBie3OjeR?= Mn[1glExKM7:TR?= NHzXPHRqdmS3Y3XzJIFxd3C2b4Ppdy=> NV;PXHA6OjN2OEK2O|E>
Glioblastoma initiating cells MkjwSpVv[3Srb36gZZN{[Xl? M2TKTp4yOCEQvF2= NGfmWppld3ewcnXneYxifGW|IITo[UBUUEhic3nncoFtcW6pIIDheIh4[Xl? NVzLT|BIOjN2OEK2O|E>
Glioblastoma initiating cells MWPGeY5kfGmxbjDhd5NigQ>? M1e4Xp4yOCEQvF2= MXrJcohq[mm2czD0bIUhTXiycnXzd4lwdiCxZjDH[Y5meyCLbo\vcJZm\CCrbjDNZYlvfGGrbnnu[{BRdHW{aYDveIVv[3l? MoXtNlM1QDJ4N{G=
Glioblastoma initiating cells MYfGeY5kfGmxbjDhd5NigQ>? M4nmXZ4yOCEQvF2= NGXwXYtKdmirYnn0d{BOd3SrbHn0fUwhUW64YYPpc44tKGGwZDDNbYdz[XSrb36= NGrid|kzOzR6Mk[3NS=>
LOX IMVI M37JOmZ2dmO2aX;uJIF{e2G7 NFvBWlAyOCEQvF2= NHO0OlJFVVOR MkDtbY5pcWKrdIOgTIVl\2Wqb3etS2xKKHCjdHj3ZZk> MnTuNlM6OzV7MkW=
UACC 257 MmnBSpVv[3Srb36gZZN{[Xl? NH3lfoMyOCEQvF2= NEHWfXFFVVOR MUfpcohq[mm2czDI[YRo\WixZz3HUGkheGG2aIfhfS=> M2jqOVI{QTN3OUK1
LOX IMVI NYjPeoI6TnWwY4Tpc44h[XO|YYm= NUT6U2tEOTBizszN MY\EUXNQ M3Tpeolv\HWlZYOgS|Eh[2WubDDjfYNt\SCjcoLld5Q> MWSyN|k{PTl{NR?=
UACC 257 M1q0VGZ2dmO2aX;uJIF{e2G7 MV[xNEDPxE1? MXjEUXNQ MXjpcoR2[2W|IFexJINmdGxiY4njcIUh[XK{ZYP0 NGGwbVQzOzl|NUmyOS=>
LOX IMVI NFXOeVJEgXSxeHnjbZR6KGG|c3H5 NHfNZpcyOCEQvF2= NXLSe3R1TE2VTx?= NHzrR2Jl\WO{ZXHz[ZMhfHWvb4KgZ4VtdCC4aXHibYxqfHl? MlfiNlM6OzV7MkW=
UACC 257 MmDUR5l1d3irY3n0fUBie3OjeR?= MVKxNEDPxE1? MU\EUXNQ NGft[YFl\WO{ZXHz[ZMhfHWvb4KgZ4VtdCC4aXHibYxqfHl? NVnOdItDOjN7M{W5NlU>
LOX IMVI NFT6ZYtCeG:ydH;zbZMh[XO|YYm= NYXvfpFiOTBizszN M3fLeGROW09? NGPOW3ZqdmS3Y3XzJIFxd3C2b4Ppdy=> NFLQbYMzOzl|NUmyOS=>
UACC 257 NWDiZpVOSXCxcITvd4l{KGG|c3H5 MkG3NVAh|ryP MX3EUXNQ MVTpcoR2[2W|IHHwc5B1d3Orcx?= Ml;vNlM6OzV7MkW=
ACHN NFvITGpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M1jBcp42KM7:TR?= NV3DdnRXTE2VTx?= NWrHV3Z6UUN3ME2yMVPjiIoQvF2= MoHnNlUxQTN2OUG=
769-P MYPHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NFXUZlV,PSEQvF2= NV:0d3o5TE2VTx?= NHfhfmRKSzVyPUKtN-KBkc7:TR?= MUWyOVA6OzR7MR?=
786-O NV6zN2t5T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M2X5dp42KM7:TR?= NH;ZPVBFVVOR MWrJR|UxRTJvM,MAje69VQ>? M1Lzd|I2ODl|NEmx
786-O SuR M3XlWWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M4rFS542KM7:TR?= M{P6WGROW09? NX7lc2ZkUUN3ME2yMVPjiIoQvF2= MUOyOVA6OzR7MR?=
SP53 M4DneGZ2dmO2aX;uJIF{e2G7 MnXHN|Ah|ryP M4HUeWROW09? Mn3UbY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u NXXUVY0xOjZ6OEW2NFg>
SP53 M2rXVmZ2dmO2aX;uJIF{e2G7 M1zuV|MxKM7:TR?= MWLEUXNQ M1PKU4lvcGmkaYTzJJRp\SCYTFG0MY1m\GmjdHXkJGZCUyC|aXfuZYxqdmdicHH0bJdigQ>? M2fSSVI3QDh3NkC4
HS5 NYLkS5pLTnWwY4Tpc44h[XO|YYm= MkC1N|Ah|ryP MlLuSG1UVw>? M3j1PIlvcGmkaYTzJINmdGxiYXTo[ZNqd25iYX7kJI1q\3KjdHnvci=> MnLVNlY5QDV4MEi=
HS27a Mm\FSpVv[3Srb36gZZN{[Xl? M4O2V|MxKM7:TR?= NF\ITFdFVVOR NXXvfW5zcW6qaXLpeJMh[2WubDDh[Ihme2mxbjDhcoQhdWmpcnH0bY9v M162dFI3QDh3NkC4
SP53 NX;jVVBpS3m2b4jpZ4l1gSCjc4PhfS=> NGHKRmM{OCEQvF2= NXuye4FWTE2VTx?= NXzVV2ppcW6mdXPld{BifXSxcHjh[5k> NIj1TJYzPjh6NU[wPC=>
Jeko MXvDfZRwgGmlaYT5JIF{e2G7 NVz0dldpOzBizszN MnPGSG1UVw>? MnvTbY5lfWOnczDheZRweGijZ4m= MUOyOlg5PTZyOB?=

多くの細胞株試験データを見る場合、クリックしてください

体内試験 Sonidegib (Erismodegib, NVP-LDE225) is highly bound to mouse, rat, and human plasma proteins (>99%) and moderately bound to dog and monkey plasma proteins (77 and 85%, respectively). LDE225 has high permeability (90.8% in man) in the PAMPA assay. LDE225 shows good oral bioavailability ranging from 69 to 102% in preclinical species when dosed in solution. LDE225 is a weak base with a measured pKa of 4.20 and exhibits relatively poor aqueous solubility. LDE225 demonstrates dose-related antitumor activity. At a dose of 5 mg/kg/day qd, LDE225 significantly inhibits tumor growth, corresponding to a T/C value of 33%. When dosed at 10 and 20 mg/kg/day qd, LDE225 gives rise to 51 and 83% regression, respectively. Gli1 mRNA inhibition correlates with tumor and plasma exposure of LDE225. LDE225 successfully penetrates the blood−brain barrier in tumor-bearing animals and results in tumor growth inhibition after 4 days of treatment. [1] LDE225 significantly reduces the tumor volume by 95.7% in Rip1-Tag2 mice. LDE225 prolongs survival in Rip1Tag2 mice. LDE225 decreases expression of stromal markers in the LDE225-treated mice. [2]

お薦めの試験操作(参考用のみ)

細胞試験:

[1]

+ 展開
  • 細胞株: TM3Hh12 cells
  • 濃度: ~10 μM
  • 反応時間: 30 minutes
  • 実験の流れ:

    LDE225 is prepared for assay by serial dilution in DMSO and then added to empty assay plates. TM3Hh12 cells (TM3 cells containing Hh-responsive reporter gene construct pTA-8xGli-Luc) are cultured in F12 Ham's/DMEM (1:1) containing 5% horse serum, 2.5% fetal bovine serum (FBS), and 15 mM HEPES, pH 7.3. Cells are harvested by trypsin treatment, resuspended in F12 Ham's/DMEM (1:1) containing 5% horse serum and 15 mM HEPES, pH 7.3, added to assay plates, and incubated with LDE225 for approximately 30 min at 37 °C in 5% CO2. Then 1 nM or 25 nM Ag1.5 is added to assay plates and incubated at 37 °C in the presence of 5% CO2. After 48 hours, either Bright-Glo or MTS reagent is added to the assay plates and luminescence or absorbance at 492 nm is determined. IC50 values, defined as the inflection point of the logistic curve, are determined by nonlinear regression of the Gli-driven luciferase luminescence or absorbance signal from MTS assay vs log10 (concentration) of LDE225 using the R statistical software pack


    (参考用のみ)
動物試験:

[1]

+ 展開
  • 動物モデル: Orthotopic Ptch+/-p53-/- medulloblastoma allograft model in athymic nude mice
  • 製剤: 0.5% sodium carboxymethyl cellulose
  • 投薬量: 40 mg/kg/day
  • 投与方法: Administered via p.o. or b.i.d
    (参考用のみ)

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 左から(NMPから)右の順に溶剤を製品に加えます:
2% DMSO+corn oil
混合させたのち直ちに使用することを推奨します。
10mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 485.5
化学式

C26H26F3N3O3

CAS No. 956697-53-3
保管
別名

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01787552 Active, not recruiting Primary Myelofibrosis|Thrombocythemia, Essential|Thrombocytosis|Myeloproliferative Disorders|Bone Marrow Diseases|Hematologic Diseases|Blood Coagulation Disorders|Blood Platelet Disorders|Hemorrhagic Disorders Novartis Pharmaceuticals|Novartis May 8, 2013 Phase 1|Phase 2
NCT02254551 Terminated Multiple Myeloma SCRI Development Innovations, LLC|Novartis January 2015 Phase 2
NCT02138929 Recruiting Esophageal Cancer M.D. Anderson Cancer Center|Novartis|National Cancer Institute (NCI) November 2014 Phase 1
NCT02195973 Active, not recruiting Recurrent Ovarian Cancer University of Alabama at Birmingham|Novartis Pharmaceuticals September 2014 Phase 1
NCT02151864 Recruiting Hepatocellular Carcinoma|Cirrhosis Jason K. Sicklick, M.D.|Novartis Pharmaceuticals|University of California, San Diego July 2014 Phase 1
NCT02182622 Unknown status Prostate Cancer Martin Gutierrez|Novartis|Hackensack University Medical Center July 2014 Phase 1

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

  • * 必須

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID