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 MX\DfZRwgGmlaYT5JIF{e2G7 NYLjXVNDhjFyIN88US=> Mn;hTWM2OD1zMjFOwG0> MlPPNlI2PTN|NUW=
A2780cp20 M3vVbWN6fG:6aXPpeJkh[XO|YYm= MXP+NVAh|ryP NEnQZ3BKSzVyPUeuOUDPxE1? MUCyNlU2OzN3NR?=
SKOV3ip1 MlXwR5l1d3irY3n0fUBie3OjeR?= M2DDVp4yOCEQvF2= MU\JR|UxRTJ2IN88US=> NH;1RYgzOjV3M{O1OS=>
SKOV3TRip2 MVXDfZRwgGmlaYT5JIF{e2G7 M2X5eJ4yOCEQvF2= NVjpWYk6UUN3ME2xNkDPxE1? MmrzNlI2PTN|NUW=
HeyA8 NHfmVGJEgXSxeHnjbZR6KGG|c3H5 NVf1cZF7hjFyIN88US=> MlXKTWM2OD1zODFOwG0> NE\Ze5QzOjV3M{O1OS=>
HeyA8MDR NH60bHdEgXSxeHnjbZR6KGG|c3H5 MXL+NVAh|ryP NUXqb2VVUUN3ME24JO69VQ>? Ml:4NlI2PTN|NUW=
OS5 Ml3FS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NHLDfWF,PSEQvF2= MWny[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w NInBd5czOzJ2M{W5OS=>
OS18 M3joemdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MYj+OUDPxE1? M1TidJJm\HWlZYOgeIhmKHC{b3zp[oVz[XSrb36= MYWyN|I1OzV7NR?=
Glioblastoma initiating cells Moq0R5l1d3irY3n0fUBie3OjeR?= NXHDblBohjFyIN88US=> M3S3e2lvcGmkaYTzJGNmdGxiVnnhZoltcXS7 NEflfWYzOzR6Mk[3NS=>
Glioblastoma initiating cells NHTPRmRHfW6ldHnvckBie3OjeR?= MlfTglExKM7:TR?= M4LxbIlvcGmkaYTzJI5mfXKxc4Do[ZJmKG[xcn3heIlwdg>? NFXiS4gzOzR6Mk[3NS=>
Glioblastoma initiating cells Mn:1R5l1d3irY3n0fUBie3OjeR?= NGD2Z3l,OTBizszN MmTtbY5lfWOnczDhdI9xfG:|aYO= M1vLUlI{PDh{Nkex
Glioblastoma initiating cells MkjTSpVv[3Srb36gZZN{[Xl? MlrYglExKM7:TR?= M{jzNoRwf26{ZXf1cIF1\XNidHjlJHNJUCC|aXfuZYxqdmdicHH0bJdigQ>? MX:yN|Q5OjZ5MR?=
Glioblastoma initiating cells MYnGeY5kfGmxbjDhd5NigQ>? NHXLWXJ,OTBizszN NESyS3BKdmirYnn0d{B1cGViRYjwdoV{e2mxbjDv[kBI\W6nczDJcpZwdH[nZDDpckBO[WmwdHHpcolv\yCSbIXybZBwfGWwY4m= NWfUPFJ5OjN2OEK2O|E>
Glioblastoma initiating cells MWTGeY5kfGmxbjDhd5NigQ>? NGL4VWh,OTBizszN Ml\CTY5pcWKrdIOgUY91cWyrdImsJGlvfmG|aX;uMEBidmRiTXnndoF1cW:w NFXXdlUzOzR6Mk[3NS=>
LOX IMVI MXfGeY5kfGmxbjDhd5NigQ>? MlnnNVAh|ryP NIPERmtFVVOR MkCxbY5pcWKrdIOgTIVl\2Wqb3etS2xKKHCjdHj3ZZk> MVGyN|k{PTl{NR?=
UACC 257 NVXWOnFDTnWwY4Tpc44h[XO|YYm= MW[xNEDPxE1? NEXKUlJFVVOR NIjFOFFqdmirYnn0d{BJ\WSpZXjv[{1IVElicHH0bJdigQ>? NFTpRmYzOzl|NUmyOS=>
LOX IMVI NX7S[XBFTnWwY4Tpc44h[XO|YYm= M2LXVlExKM7:TR?= Ml;NSG1UVw>? Ml2zbY5lfWOnczDHNUBk\WyuIHP5Z4xmKGG{cnXzeC=> MY[yN|k{PTl{NR?=
UACC 257 MYTGeY5kfGmxbjDhd5NigQ>? NHzDVnUyOCEQvF2= MWnEUXNQ NXfvRopCcW6mdXPld{BIOSClZXzsJIN6[2ynIHHydoV{fA>? MkCxNlM6OzV7MkW=
LOX IMVI NXH5OYZ4S3m2b4jpZ4l1gSCjc4PhfS=> MYexNEDPxE1? Mn23SG1UVw>? M4jsbYRm[3KnYYPld{B1fW2xcjDj[YxtKH[rYXLpcIl1gQ>? MYeyN|k{PTl{NR?=
UACC 257 MVvDfZRwgGmlaYT5JIF{e2G7 MnnZNVAh|ryP NWCzXVFlTE2VTx?= MX;k[YNz\WG|ZYOgeJVud3JiY3XscEB3cWGkaXzpeJk> MoftNlM6OzV7MkW=
LOX IMVI MV\BdI9xfG:|aYOgZZN{[Xl? M3\tdFExKM7:TR?= NHTSPFhFVVOR NEH1d4pqdmS3Y3XzJIFxd3C2b4Ppdy=> NG\NPG4zOzl|NUmyOS=>
UACC 257 NUC4d4FESXCxcITvd4l{KGG|c3H5 M1rCUVExKM7:TR?= NXPSUYZzTE2VTx?= M1zPXolv\HWlZYOgZZBweHSxc3nz M1jUbFI{QTN3OUK1
ACHN NH3nbWlIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NXHqZVZ2hjVizszN M1jFfmROW09? Mn;zTWM2OD1{LURihKnPxE1? NGTpR5czPTB7M{S5NS=>
769-P MVHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MXL+OUDPxE1? MYjEUXNQ NYDDW48{UUN3ME2yMVPjiIoQvF2= MoLhNlUxQTN2OUG=
786-O NIfIVWtIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NUDrNWV2hjVizszN MmHISG1UVw>? MmTtTWM2OD1{LURihKnPxE1? MXGyOVA6OzR7MR?=
786-O SuR NH\kUJdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MXn+OUDPxE1? M2HjfmROW09? M1vNe2lEPTB;Mj2z5qCK|ryP NIHVe3QzPTB7M{S5NS=>
SP53 MX3GeY5kfGmxbjDhd5NigQ>? NHnZdIg{OCEQvF2= NYqxRXdqTE2VTx?= Mme1bY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u NX7xS5pkOjZ6OEW2NFg>
SP53 MmX4SpVv[3Srb36gZZN{[Xl? MV[zNEDPxE1? MYDEUXNQ Mn\XbY5pcWKrdIOgeIhmKF[OQUStcYVlcWG2ZXSgSmFMKHOrZ37hcIlv\yCyYYToe4F6 NF7jW4UzPjh6NU[wPC=>
HS5 NWO3UGZxTnWwY4Tpc44h[XO|YYm= MYqzNEDPxE1? NH;QeVRFVVOR Mn\wbY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u NEXwN3AzPjh6NU[wPC=>
HS27a NEfCVIZHfW6ldHnvckBie3OjeR?= NHXST3o{OCEQvF2= M4e4bGROW09? MWPpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= MlnmNlY5QDV4MEi=
SP53 M{DMUmN6fG:6aXPpeJkh[XO|YYm= MUWzNEDPxE1? MmjTSG1UVw>? M2fTfIlv\HWlZYOgZZV1d3CqYXf5 M{O3SFI3QDh3NkC4
Jeko NIq4PWpEgXSxeHnjbZR6KGG|c3H5 NHz6b5U{OCEQvF2= MVvEUXNQ M3[0eIlv\HWlZYOgZZV1d3CqYXf5 NUDQRWxyOjZ6OEW2NFg>

他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

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(文献ではなく、Selleckの実験によるデータ):
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
in solvent
別名

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    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

貯蔵液を準備するために必要な希釈率を計算してください。Selleck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 ( 入力 出力 )

  • 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

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01787552 Completed 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
NCT01708174 Completed Medulloblastoma Novartis Pharmaceuticals|Novartis May 6 2013 Phase 2
NCT02254551 Terminated Multiple Myeloma SCRI Development Innovations LLC|Novartis January 2015 Phase 2
NCT02195973 Completed Recurrent Ovarian Cancer University of Alabama at Birmingham|Novartis Pharmaceuticals September 2014 Phase 1
NCT02182622 Unknown status Prostate Cancer Martin Gutierrez|Novartis|Hackensack Meridian Health July 2014 Phase 1
NCT02151864 Active not recruiting Hepatocellular Carcinoma|Cirrhosis Jason K. Sicklick M.D.|Novartis Pharmaceuticals|University of California San Diego 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

Hedgehog/Smoothenedシグナル伝達経路

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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