Sonidegib (Erismodegib, NVP-LDE225)

Catalog No.S2151

Sonidegib (Erismodegib, NVP-LDE225) Chemical Structure

Molecular Weight(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.

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Cited by 15 Publications

3 Customer Reviews

  • 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.

  • 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.

Purity & Quality Control

Choose Selective Hedgehog/Smoothened Inhibitors

Biological Activity

Description 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.
Targets
Smo (mouse) [1]
(Cell-free assay)
Smo (human) [1]
(Cell-free assay)
1.3 nM 2.5 nM
In vitro

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780ip2 MU\DfZRwgGmlaYT5JIF{e2G7 NHTO[5l,OTBizszN MnXITWM2OD1zMjFOwG0> MXuyNlU2OzN3NR?=
A2780cp20 NFj3T3FEgXSxeHnjbZR6KGG|c3H5 NEnoRo1,OTBizszN MV;JR|UxRTdwNTFOwG0> MoLyNlI2PTN|NUW=
SKOV3ip1 MVTDfZRwgGmlaYT5JIF{e2G7 MUD+NVAh|ryP M1O1[2lEPTB;MkSg{txO MnnVNlI2PTN|NUW=
SKOV3TRip2 NFXKcoVEgXSxeHnjbZR6KGG|c3H5 M4DjWZ4yOCEQvF2= NEfRR5hKSzVyPUGyJO69VQ>? NFTBe|EzOjV3M{O1OS=>
HeyA8 NXHLd21QS3m2b4jpZ4l1gSCjc4PhfS=> NVTYPIR4hjFyIN88US=> NGPITo9KSzVyPUG4JO69VQ>? M3jaeVIzPTV|M{W1
HeyA8MDR NWTaS|dSS3m2b4jpZ4l1gSCjc4PhfS=> MmPZglExKM7:TR?= MkexTWM2OD16IN88US=> MV2yNlU2OzN3NR?=
OS5 NY\aeoNQT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NGjoU4l,PSEQvF2= M1jyW5Jm\HWlZYOgeIhmKHC{b3zp[oVz[XSrb36= NY\0Z5BUOjN{NEO1PVU>
OS18 M13rVGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NYPxNnZ5hjVizszN NV;pS5RMemWmdXPld{B1cGVicILvcIln\XKjdHnvci=> NVLpXY84OjN{NEO1PVU>
Glioblastoma initiating cells M1Tae2N6fG:6aXPpeJkh[XO|YYm= MmHpglExKM7:TR?= Mk\rTY5pcWKrdIOgR4VtdCCYaXHibYxqfHl? MkjUNlM1QDJ4N{G=
Glioblastoma initiating cells NF7pdXpHfW6ldHnvckBie3OjeR?= MYD+NVAh|ryP M4PFWIlvcGmkaYTzJI5mfXKxc4Do[ZJmKG[xcn3heIlwdg>? MXmyN|Q5OjZ5MR?=
Glioblastoma initiating cells MomyR5l1d3irY3n0fUBie3OjeR?= MYf+NVAh|ryP NXr5VGR[cW6mdXPld{BieG:ydH;zbZM> NI\DUG8zOzR6Mk[3NS=>
Glioblastoma initiating cells NVP0[WRKTnWwY4Tpc44h[XO|YYm= Mnv1glExKM7:TR?= M3HP[IRwf26{ZXf1cIF1\XNidHjlJHNJUCC|aXfuZYxqdmdicHH0bJdigQ>? MnvUNlM1QDJ4N{G=
Glioblastoma initiating cells M33MZ2Z2dmO2aX;uJIF{e2G7 NHrqcpF,OTBizszN NHnodWxKdmirYnn0d{B1cGViRYjwdoV{e2mxbjDv[kBI\W6nczDJcpZwdH[nZDDpckBO[WmwdHHpcolv\yCSbIXybZBwfGWwY4m= NGrrRZozOzR6Mk[3NS=>
Glioblastoma initiating cells NHjpSlZHfW6ldHnvckBie3OjeR?= MX3+NVAh|ryP MYfJcohq[mm2czDNc5RqdGm2eTygTY53[XOrb36sJIFv\CCPaXfyZZRqd25? NIPIXHkzOzR6Mk[3NS=>
LOX IMVI M1T0O2Z2dmO2aX;uJIF{e2G7 NITKXFIyOCEQvF2= Ml:xSG1UVw>? M1HpfYlvcGmkaYTzJGhm\GenaH;nMWdNUSCyYYToe4F6 NIn2U|czOzl|NUmyOS=>
UACC 257 NYLSdHR1TnWwY4Tpc44h[XO|YYm= NH7hTHkyOCEQvF2= MULEUXNQ NHz0[GhqdmirYnn0d{BJ\WSpZXjv[{1IVElicHH0bJdigQ>? M3PzXVI{QTN3OUK1
LOX IMVI NULPb|BwTnWwY4Tpc44h[XO|YYm= M1vSfVExKM7:TR?= MUjEUXNQ NIDEWIFqdmS3Y3XzJGcyKGOnbHygZ5lkdGViYYLy[ZN1 NF7ub4wzOzl|NUmyOS=>
UACC 257 MkLPSpVv[3Srb36gZZN{[Xl? MWGxNEDPxE1? NWW4box5TE2VTx?= Ml\BbY5lfWOnczDHNUBk\WyuIHP5Z4xmKGG{cnXzeC=> MXGyN|k{PTl{NR?=
LOX IMVI MXvDfZRwgGmlaYT5JIF{e2G7 NX36TmxsOTBizszN MmewSG1UVw>? NFLEUVJl\WO{ZXHz[ZMhfHWvb4KgZ4VtdCC4aXHibYxqfHl? M1K3NFI{QTN3OUK1
UACC 257 M1XNSWN6fG:6aXPpeJkh[XO|YYm= M1jDeFExKM7:TR?= M4fSZmROW09? M1rwZoRm[3KnYYPld{B1fW2xcjDj[YxtKH[rYXLpcIl1gQ>? NYfndW5qOjN7M{W5NlU>
LOX IMVI MlnBRZBweHSxc3nzJIF{e2G7 NYXvOJI3OTBizszN MXXEUXNQ MXrpcoR2[2W|IHHwc5B1d3Orcx?= MX[yN|k{PTl{NR?=
UACC 257 MkDpRZBweHSxc3nzJIF{e2G7 NWTZcJhnOTBizszN MmH4SG1UVw>? MmDlbY5lfWOnczDhdI9xfG:|aYO= M4ryOFI{QTN3OUK1
ACHN NGrUN4lIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NYW2XVBPhjVizszN MUDEUXNQ M3HDWGlEPTB;Mj2z5qCK|ryP MVSyOVA6OzR7MR?=
769-P MVLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M1zyUZ42KM7:TR?= NG[1U2dFVVOR NH3PXJRKSzVyPUKtN-KBkc7:TR?= MVKyOVA6OzR7MR?=
786-O NHHr[mZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NUfrVnRLhjVizszN NYjINGZ5TE2VTx?= MXTJR|UxRTJvM,MAje69VQ>? MXeyOVA6OzR7MR?=
786-O SuR MUTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M1PYUJ42KM7:TR?= NEXvTpFFVVOR Ml3hTWM2OD1{LURihKnPxE1? MXGyOVA6OzR7MR?=
SP53 Mnf2SpVv[3Srb36gZZN{[Xl? MWOzNEDPxE1? MV\EUXNQ MWPpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= MkXtNlY5QDV4MEi=
SP53 NVG5S4FZTnWwY4Tpc44h[XO|YYm= MW[zNEDPxE1? M1vDTGROW09? NWi5WVU2cW6qaXLpeJMhfGinIG\MRVQudWWmaXH0[YQhTkGNIIPp[45idGmwZzDwZZRpf2G7 M2nZdFI3QDh3NkC4
HS5 NU[0bZBjTnWwY4Tpc44h[XO|YYm= MWKzNEDPxE1? MVnEUXNQ MXfpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= NGXHT2ozPjh6NU[wPC=>
HS27a MYLGeY5kfGmxbjDhd5NigQ>? M3yxUVMxKM7:TR?= MmTmSG1UVw>? M1jXS4lvcGmkaYTzJINmdGxiYXTo[ZNqd25iYX7kJI1q\3KjdHnvci=> NWXMPFc2OjZ6OEW2NFg>
SP53 MoHrR5l1d3irY3n0fUBie3OjeR?= MnPpN|Ah|ryP NXTMVZZ4TE2VTx?= M4\mZolv\HWlZYOgZZV1d3CqYXf5 M{jxS|I3QDh3NkC4
Jeko MmrlR5l1d3irY3n0fUBie3OjeR?= MX2zNEDPxE1? NYrjSXRkTE2VTx?= MnnzbY5lfWOnczDheZRweGijZ4m= M3fFTFI3QDh3NkC4

... 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
In vivo 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]

Protocol

Cell Research:

[1]

+ Expand
  • Cell lines: TM3Hh12 cells
  • Concentrations: ~10 μM
  • Incubation Time: 30 minutes
  • Method:

    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


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: Orthotopic Ptch+/-p53-/- medulloblastoma allograft model in athymic nude mice
  • Formulation: 0.5% sodium carboxymethyl cellulose
  • Dosages: 40 mg/kg/day
  • Administration: Administered via p.o. or b.i.d
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 97 mg/mL (199.79 mM)
Ethanol 97 mg/mL warmed (199.79 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+corn oil
For best results, use promptly after mixing.
10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 485.5
Formula

C26H26F3N3O3

CAS No. 956697-53-3
Storage powder
in solvent
Synonyms

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Clinical Trial Information

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID