LDE225 (NVP-LDE225,Erismodegib)

Catalog No.S2151 Synonyms: Sonidegib

LDE225 (NVP-LDE225,Erismodegib) Chemical Structure

Molecular Weight(MW): 485.5

LDE225 (NVP-LDE225,Erismodegib) 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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In DMSO USD 210 In stock
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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. LDE225 (NVP-LDE225,Erismodegib) 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. LDE225 (NVP-LDE225,Erismodegib) 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. LDE225 (NVP-LDE225,Erismodegib) purchased from Selleck.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description LDE225 (NVP-LDE225,Erismodegib) 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

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 MoXHR5l1d3irY3n0fUBie3OjeR?= MnvVglExKM7:TR?= NHS5WFhKSzVyPUGyJO69VQ>? MYGyNlU2OzN3NR?=
A2780cp20 Mn\iR5l1d3irY3n0fUBie3OjeR?= MkLHglExKM7:TR?= MkHPTWM2OD15LkWg{txO MkDENlI2PTN|NUW=
SKOV3ip1 MUfDfZRwgGmlaYT5JIF{e2G7 NYXIUFE{hjFyIN88US=> MoO0TWM2OD1{NDFOwG0> MUiyNlU2OzN3NR?=
SKOV3TRip2 NY\VTnd6S3m2b4jpZ4l1gSCjc4PhfS=> MmrpglExKM7:TR?= M1\tOWlEPTB;MUKg{txO NESwWlEzOjV3M{O1OS=>
HeyA8 M2mxZWN6fG:6aXPpeJkh[XO|YYm= M1z3VJ4yOCEQvF2= NUTjUoVWUUN3ME2xPEDPxE1? M1LrOVIzPTV|M{W1
HeyA8MDR NVnVeopSS3m2b4jpZ4l1gSCjc4PhfS=> NF\VZZR,OTBizszN NH3QZWtKSzVyPUig{txO MUKyNlU2OzN3NR?=
OS5 Mk\LS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MlH0glUh|ryP MWLy[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w NUThSoVpOjN{NEO1PVU>
OS18 M1\NN2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MlTpglUh|ryP MVfy[YR2[2W|IITo[UBxem:uaX\ldoF1cW:w MYKyN|I1OzV7NR?=
Glioblastoma initiating cells NIPmb4xEgXSxeHnjbZR6KGG|c3H5 M{DZ[Z4yOCEQvF2= NULyfo82UW6qaXLpeJMhS2WubDDWbYFjcWyrdIm= NXHDeWd{OjN2OEK2O|E>
Glioblastoma initiating cells NHjleI9HfW6ldHnvckBie3OjeR?= MknaglExKM7:TR?= NY\pSmhvcW6qaXLpeJMhdmW3cn;zdIhmemViZn;ycYF1cW:w NHXQeYgzOzR6Mk[3NS=>
Glioblastoma initiating cells NGflRY5EgXSxeHnjbZR6KGG|c3H5 NVexZ29lhjFyIN88US=> MnLIbY5lfWOnczDhdI9xfG:|aYO= NHXsTWszOzR6Mk[3NS=>
Glioblastoma initiating cells M3r6dGZ2dmO2aX;uJIF{e2G7 MmK3glExKM7:TR?= Mo\I[I94dnKnZ4XsZZRmeyC2aHWgV2hJKHOrZ37hcIlv\yCyYYToe4F6 M1W3XVI{PDh{Nkex
Glioblastoma initiating cells MnjpSpVv[3Srb36gZZN{[Xl? MUn+NVAh|ryP NIfX[2RKdmirYnn0d{B1cGViRYjwdoV{e2mxbjDv[kBI\W6nczDJcpZwdH[nZDDpckBO[WmwdHHpcolv\yCSbIXybZBwfGWwY4m= NF\0XpIzOzR6Mk[3NS=>
Glioblastoma initiating cells NULpVVBDTnWwY4Tpc44h[XO|YYm= MVH+NVAh|ryP M{Xs[2lvcGmkaYTzJG1wfGmuaYT5MEBKdn[jc3nvckwh[W6mIF3p[5JifGmxbh?= NHSyVlMzOzR6Mk[3NS=>
LOX IMVI M3jTN2Z2dmO2aX;uJIF{e2G7 M1jIeFExKM7:TR?= MX;EUXNQ MVnpcohq[mm2czDI[YRo\WixZz3HUGkheGG2aIfhfS=> NWfZWnJOOjN7M{W5NlU>
UACC 257 NILHcIVHfW6ldHnvckBie3OjeR?= NXX1bnZ2OTBizszN MkDBSG1UVw>? M2\WOYlvcGmkaYTzJGhm\GenaH;nMWdNUSCyYYToe4F6 M3vJWVI{QTN3OUK1
LOX IMVI NYjO[Y05TnWwY4Tpc44h[XO|YYm= M3T3eVExKM7:TR?= Mn\LSG1UVw>? NEW0O5BqdmS3Y3XzJGcyKGOnbHygZ5lkdGViYYLy[ZN1 MWOyN|k{PTl{NR?=
UACC 257 NInw[ppHfW6ldHnvckBie3OjeR?= NITqdmYyOCEQvF2= MlnlSG1UVw>? MV7pcoR2[2W|IFexJINmdGxiY4njcIUh[XK{ZYP0 NY\leIY4OjN7M{W5NlU>
LOX IMVI MnrKR5l1d3irY3n0fUBie3OjeR?= NULQbWJkOTBizszN M{LIOGROW09? M2\FT4Rm[3KnYYPld{B1fW2xcjDj[YxtKH[rYXLpcIl1gQ>? NHfKVIkzOzl|NUmyOS=>
UACC 257 NGfIRlJEgXSxeHnjbZR6KGG|c3H5 M1nSWVExKM7:TR?= NVvYVlFpTE2VTx?= NEXU[Yll\WO{ZXHz[ZMhfHWvb4KgZ4VtdCC4aXHibYxqfHl? NUj0dZY4OjN7M{W5NlU>
LOX IMVI MoLjRZBweHSxc3nzJIF{e2G7 NWnQcmE1OTBizszN MXnEUXNQ MX;pcoR2[2W|IHHwc5B1d3Orcx?= M{\H[VI{QTN3OUK1
UACC 257 MXnBdI9xfG:|aYOgZZN{[Xl? MnnMNVAh|ryP MUjEUXNQ M1T1Xolv\HWlZYOgZZBweHSxc3nz NF;SW3ozOzl|NUmyOS=>
ACHN MULHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NG\oeFl,PSEQvF2= Mn3FSG1UVw>? NGKzb|hKSzVyPUKtN-KBkc7:TR?= MVSyOVA6OzR7MR?=
769-P NGK5bHdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NFXnOnR,PSEQvF2= M37uNWROW09? NHzteoxKSzVyPUKtN-KBkc7:TR?= M37XZ|I2ODl|NEmx
786-O MV\Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MWP+OUDPxE1? NF[1dG9FVVOR NIfpOnlKSzVyPUKtN-KBkc7:TR?= M2qwW|I2ODl|NEmx
786-O SuR NGS1XIVIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NH7WVZB,PSEQvF2= NEDP[HBFVVOR MXzJR|UxRTJvM,MAje69VQ>? NHXucY4zPTB7M{S5NS=>
SP53 NIrGeVdHfW6ldHnvckBie3OjeR?= MnTJN|Ah|ryP NHW3[4xFVVOR MXHpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= NIPoSJQzPjh6NU[wPC=>
SP53 MlTZSpVv[3Srb36gZZN{[Xl? NHzUT5g{OCEQvF2= NFe3WGtFVVOR MmLWbY5pcWKrdIOgeIhmKF[OQUStcYVlcWG2ZXSgSmFMKHOrZ37hcIlv\yCyYYToe4F6 M3KyNVI3QDh3NkC4
HS5 MVHGeY5kfGmxbjDhd5NigQ>? M2r2T|MxKM7:TR?= NEXCVVZFVVOR M1XXRYlvcGmkaYTzJINmdGxiYXTo[ZNqd25iYX7kJI1q\3KjdHnvci=> M{fPO|I3QDh3NkC4
HS27a MnGySpVv[3Srb36gZZN{[Xl? NE\v[28{OCEQvF2= MVvEUXNQ NF3YZXBqdmirYnn0d{Bk\WyuIHHkbIV{cW:wIHHu[EBucWe{YYTpc44> M4\QdFI3QDh3NkC4
SP53 MVnDfZRwgGmlaYT5JIF{e2G7 NGLDUI0{OCEQvF2= M3Pw[WROW09? Mnz5bY5lfWOnczDheZRweGijZ4m= Ml;ZNlY5QDV4MEi=
Jeko M4r3SmN6fG:6aXPpeJkh[XO|YYm= Ml;yN|Ah|ryP M{PiV2ROW09? NHzwOmlqdmS3Y3XzJIF2fG:yaHHnfS=> MmHNNlY5QDV4MEi=

... Click to View More Cell Line Experimental Data

In vivo 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 <1 mg/mL
In vivo 2% DMSO+corn oil 10mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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 Sonidegib

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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