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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3 Customer Reviews

  • 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.

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.
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 M4\yb2N6fG:6aXPpeJkh[XO|YYm= M4S4bp4yOCEQvF2= NV;6O5NmUUN3ME2xNkDPxE1? NFX1UWczOjV3M{O1OS=>
A2780cp20 MYHDfZRwgGmlaYT5JIF{e2G7 NHPpVGR,OTBizszN NHjmfFNKSzVyPUeuOUDPxE1? M2ToblIzPTV|M{W1
SKOV3TRip2 NXz2[HExS3m2b4jpZ4l1gSCjc4PhfS=> MWr+NVAh|ryP M{nrOWlEPTB;MUKg{txO NH7WfXIzOjV3M{O1OS=>
HeyA8MDR NUXvOXBvS3m2b4jpZ4l1gSCjc4PhfS=> MXz+NVAh|ryP MkjqTWM2OD16IN88US=> NEnCbHYzOjV3M{O1OS=>
OS5 NV;n[lNlT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MmPFglUh|ryP NIO1fmlz\WS3Y3XzJJRp\SCycn;sbYZmemG2aX;u MXqyN|I1OzV7NR?=
OS18 MlrTS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NEPLcGt,PSEQvF2= MWPy[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w NXT4V4pxOjN{NEO1PVU>
Glioblastoma initiating cells MnzXR5l1d3irY3n0fUBie3OjeR?= NFrXZm5,OTBizszN MWXJcohq[mm2czDD[YxtKF[rYXLpcIl1gQ>? MoTGNlM1QDJ4N{G=
Glioblastoma initiating cells MkDlSpVv[3Srb36gZZN{[Xl? NY\CU4wyhjFyIN88US=> NX20ZWducW6qaXLpeJMhdmW3cn;zdIhmemViZn;ycYF1cW:w MmfLNlM1QDJ4N{G=
Glioblastoma initiating cells NVPVbYxqS3m2b4jpZ4l1gSCjc4PhfS=> MX7+NVAh|ryP MVHpcoR2[2W|IHHwc5B1d3Orcx?= MoDtNlM1QDJ4N{G=
Glioblastoma initiating cells NXm0SolPTnWwY4Tpc44h[XO|YYm= MUL+NVAh|ryP M33sPIRwf26{ZXf1cIF1\XNidHjlJHNJUCC|aXfuZYxqdmdicHH0bJdigQ>? NGfTeXkzOzR6Mk[3NS=>
Glioblastoma initiating cells M3rUdmZ2dmO2aX;uJIF{e2G7 NHjnd|Z,OTBizszN NV;YXlJCUW6qaXLpeJMhfGinIFX4dJJme3Orb36gc4YhT2WwZYOgTY53d2y4ZXSgbY4hVWGrboThbY5qdmdiUHz1dolxd3SnbnP5 MlL6NlM1QDJ4N{G=
Glioblastoma initiating cells M2LSZmZ2dmO2aX;uJIF{e2G7 NV;6U4V6hjFyIN88US=> NFjIZ5VKdmirYnn0d{BOd3SrbHn0fUwhUW64YYPpc44tKGGwZDDNbYdz[XSrb36= M4DkSFI{PDh{Nkex
LOX IMVI MnzESpVv[3Srb36gZZN{[Xl? Mo\2NVAh|ryP M2PyRmROW09? M{nodYlvcGmkaYTzJGhm\GenaH;nMWdNUSCyYYToe4F6 MVKyN|k{PTl{NR?=
UACC 257 MV;GeY5kfGmxbjDhd5NigQ>? MkDYNVAh|ryP MUHEUXNQ NHzaRnhqdmirYnn0d{BJ\WSpZXjv[{1IVElicHH0bJdigQ>? M4O1ZVI{QTN3OUK1
LOX IMVI MnOwSpVv[3Srb36gZZN{[Xl? MWqxNEDPxE1? NWn6fHZQTE2VTx?= NX6z[Ho3cW6mdXPld{BIOSClZXzsJIN6[2ynIHHydoV{fA>? NYDse2d7OjN7M{W5NlU>
UACC 257 MnXzSpVv[3Srb36gZZN{[Xl? MmH1NVAh|ryP MoXySG1UVw>? NIPMb5lqdmS3Y3XzJGcyKGOnbHygZ5lkdGViYYLy[ZN1 M3nJeFI{QTN3OUK1
LOX IMVI MnL5R5l1d3irY3n0fUBie3OjeR?= NV22[4JlOTBizszN NIr3fGFFVVOR NVPDdnVE\GWlcnXhd4V{KHS3bX;yJINmdGxidnnhZoltcXS7 M4ftPFI{QTN3OUK1
UACC 257 NXLuOVBpS3m2b4jpZ4l1gSCjc4PhfS=> NXvNSXo5OTBizszN NV3KNoN1TE2VTx?= NIH3VWFl\WO{ZXHz[ZMhfHWvb4KgZ4VtdCC4aXHibYxqfHl? NXr2fYRGOjN7M{W5NlU>
UACC 257 M17rbGFxd3C2b4Ppd{Bie3OjeR?= MnPHNVAh|ryP NV;rcJpkTE2VTx?= M{LM[Ylv\HWlZYOgZZBweHSxc3nz MlXZNlM6OzV7MkW=
769-P MWjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MWX+OUDPxE1? NF;EWlJFVVOR NInaUWZKSzVyPUKtN-KBkc7:TR?= NUKzc5hpOjVyOUO0PVE>
786-O M1v3UWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NF61NWd,PSEQvF2= MUjEUXNQ NGfPe2lKSzVyPUKtN-KBkc7:TR?= M{WyPVI2ODl|NEmx
786-O SuR Mn[zS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M1fvTZ42KM7:TR?= NXHjeGRxTE2VTx?= M13ETWlEPTB;Mj2z5qCK|ryP NVjZdZdjOjVyOUO0PVE>
SP53 NYO4VGpbTnWwY4Tpc44h[XO|YYm= NEC1PGk{OCEQvF2= NX[z[JpwTE2VTx?= NVXXUHFycW6qaXLpeJMh[2WubDDh[Ihme2mxbjDhcoQhdWmpcnH0bY9v NXjSWpQyOjZ6OEW2NFg>
SP53 Mnr1SpVv[3Srb36gZZN{[Xl? MYGzNEDPxE1? NU\oXZJCTE2VTx?= MVvpcohq[mm2czD0bIUhXkyDND3t[YRq[XSnZDDGRWshe2mpbnHsbY5oKHCjdHj3ZZk> NY\2dYRwOjZ6OEW2NFg>
HS5 MnzCSpVv[3Srb36gZZN{[Xl? MoDNN|Ah|ryP NH\uWWlFVVOR MlvRbY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u NH[0ZmczPjh6NU[wPC=>
HS27a MlPCSpVv[3Srb36gZZN{[Xl? NHnxSWY{OCEQvF2= NGDsNnhFVVOR NGe5NGJqdmirYnn0d{Bk\WyuIHHkbIV{cW:wIHHu[EBucWe{YYTpc44> MlPmNlY5QDV4MEi=
SP53 NXfuWYR6S3m2b4jpZ4l1gSCjc4PhfS=> NXTIXpFtOzBizszN M2O3VGROW09? NGfSVVFqdmS3Y3XzJIF2fG:yaHHnfS=> Ml7ZNlY5QDV4MEi=
Jeko M3PIPWN6fG:6aXPpeJkh[XO|YYm= M3K2OFMxKM7:TR?= MlXNSG1UVw>? Mlv1bY5lfWOnczDheZRweGijZ4m= MonqNlY5QDV4MEi=

... Click to View More Cell Line Experimental Data

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]


Cell Research:


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  • 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:


+ 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 individually and in order:
2% DMSO+corn oil

* 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


CAS No. 956697-53-3
Storage powder

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Clinical Trial Information

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID