Sonidegib (NVP-LDE225)

For research use only. Not for use in humans.

Catalog No.S2151 Synonyms: Erismodegib

27 publications

Sonidegib (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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Selleck's Sonidegib (NVP-LDE225) has been cited by 27 publications

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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 MUnDfZRwgGmlaYT5JIF{e2G7 NH32TIt,OTBizszN NVS1WmI5UUN3ME2xNkDPxE1? NEL1[oUzOjV3M{O1OS=>
A2780cp20 NHniNpBEgXSxeHnjbZR6KGG|c3H5 MWX+NVAh|ryP NFfqN4dKSzVyPUeuOUDPxE1? NVezVVAxOjJ3NUOzOVU>
SKOV3ip1 NYjTdlE1S3m2b4jpZ4l1gSCjc4PhfS=> MXr+NVAh|ryP MWjJR|UxRTJ2IN88US=> NY\QZ2V4OjJ3NUOzOVU>
HeyA8 NY\rb4RpS3m2b4jpZ4l1gSCjc4PhfS=> NUfZVZBmhjFyIN88US=> NU\iWJN4UUN3ME2xPEDPxE1? NH\yVmwzOjV3M{O1OS=>
OS5 NXvTWGU6T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MX3+OUDPxE1? M4K2V5Jm\HWlZYOgeIhmKHC{b3zp[oVz[XSrb36= MoXINlMzPDN3OUW=
OS18 NWfUR3FRT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M{jnZ542KM7:TR?= NWrwbFJlemWmdXPld{B1cGVicILvcIln\XKjdHnvci=> NUSxVYZiOjN{NEO1PVU>
Glioblastoma initiating cells NI[4NmlEgXSxeHnjbZR6KGG|c3H5 NIWwSlF,OTBizszN NHPJS3pKdmirYnn0d{BE\WyuIG\pZYJqdGm2eR?= NXX2PVBHOjN2OEK2O|E>
Glioblastoma initiating cells NWmxfGhxTnWwY4Tpc44h[XO|YYm= MX\+NVAh|ryP NV7uVWkycW6qaXLpeJMhdmW3cn;zdIhmemViZn;ycYF1cW:w M4DIeVI{PDh{Nkex
Glioblastoma initiating cells NFLvXHdEgXSxeHnjbZR6KGG|c3H5 M2XySZ4yOCEQvF2= NUS1W2VPcW6mdXPld{BieG:ydH;zbZM> MWCyN|Q5OjZ5MR?=
Glioblastoma initiating cells M4DvZ2Z2dmO2aX;uJIF{e2G7 NHPUOIJ,OTBizszN MmH4[I94dnKnZ4XsZZRmeyC2aHWgV2hJKHOrZ37hcIlv\yCyYYToe4F6 MY[yN|Q5OjZ5MR?=
Glioblastoma initiating cells NXXZeIVjTnWwY4Tpc44h[XO|YYm= M13ZUZ4yOCEQvF2= NFX3bJVKdmirYnn0d{B1cGViRYjwdoV{e2mxbjDv[kBI\W6nczDJcpZwdH[nZDDpckBO[WmwdHHpcolv\yCSbIXybZBwfGWwY4m= M163SVI{PDh{Nkex
Glioblastoma initiating cells MojDSpVv[3Srb36gZZN{[Xl? MUn+NVAh|ryP M4HCXWlvcGmkaYTzJG1wfGmuaYT5MEBKdn[jc3nvckwh[W6mIF3p[5JifGmxbh?= NFTrRlkzOzR6Mk[3NS=>
UACC 257 MXrGeY5kfGmxbjDhd5NigQ>? MW[xNEDPxE1? NELr[XFFVVOR NWjKXYdHcW6qaXLpeJMhUGWmZ3Xoc4cuT0yLIIDheIh4[Xl? M1XyOlI{QTN3OUK1
UACC 257 NWfqfXBsTnWwY4Tpc44h[XO|YYm= NI[3dIsyOCEQvF2= Ml23SG1UVw>? NWHyV|JvcW6mdXPld{BIOSClZXzsJIN6[2ynIHHydoV{fA>? NV\jSlE2OjN7M{W5NlU>
UACC 257 MlnaR5l1d3irY3n0fUBie3OjeR?= NHPWOWMyOCEQvF2= MWLEUXNQ MUfk[YNz\WG|ZYOgeJVud3JiY3XscEB3cWGkaXzpeJk> MXGyN|k{PTl{NR?=
LOX IMVI NXy3dGVrSXCxcITvd4l{KGG|c3H5 NGn3OIYyOCEQvF2= Ml75SG1UVw>? NFHOVXVqdmS3Y3XzJIFxd3C2b4Ppdy=> Mni5NlM6OzV7MkW=
UACC 257 NU\Me4tUSXCxcITvd4l{KGG|c3H5 M3XWUFExKM7:TR?= NUe1ZVFzTE2VTx?= MnP1bY5lfWOnczDhdI9xfG:|aYO= NYnGVmlROjN7M{W5NlU>
ACHN Ml;ES5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M2LvN542KM7:TR?= NVf1d2JSTE2VTx?= MoixTWM2OD1{LURihKnPxE1? NHO0b40zPTB7M{S5NS=>
769-P Ml7MS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NIK3b2t,PSEQvF2= M3LJ[WROW09? M3rafWlEPTB;Mj2z5qCK|ryP MlHlNlUxQTN2OUG=
786-O NGjiOodIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NHvPd5J,PSEQvF2= MV\EUXNQ M2TWO2lEPTB;Mj2z5qCK|ryP M1yzRVI2ODl|NEmx
786-O SuR NHfYSYxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MV\+OUDPxE1? NH[wVoJFVVOR MVHJR|UxRTJvM,MAje69VQ>? MkHNNlUxQTN2OUG=
SP53 MULGeY5kfGmxbjDhd5NigQ>? NV3JO4I4OzBizszN M2\tfmROW09? MlTUbY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u MlWxNlY5QDV4MEi=
SP53 MULGeY5kfGmxbjDhd5NigQ>? M4rCcFMxKM7:TR?= MVzEUXNQ M{TVVolvcGmkaYTzJJRp\SCYTFG0MY1m\GmjdHXkJGZCUyC|aXfuZYxqdmdicHH0bJdigQ>? NFfJWIgzPjh6NU[wPC=>
HS5 NVX2[nZOTnWwY4Tpc44h[XO|YYm= Mmj5N|Ah|ryP M1HZUGROW09? MnXIbY5pcWKrdIOgZ4VtdCCjZHjld4lwdiCjbnSgcYloemG2aX;u NF7OfGozPjh6NU[wPC=>
HS27a NE\1ZYlHfW6ldHnvckBie3OjeR?= NFn5dGs{OCEQvF2= NVfpUHg4TE2VTx?= MYfpcohq[mm2czDj[YxtKGGmaHXzbY9vKGGwZDDtbYdz[XSrb36= NFTtTYIzPjh6NU[wPC=>
SP53 MWHDfZRwgGmlaYT5JIF{e2G7 MlzsN|Ah|ryP MUnEUXNQ NYrnOpZGcW6mdXPld{BifXSxcHjh[5k> M3nKSlI3QDh3NkC4
Jeko M3m0OGN6fG:6aXPpeJkh[XO|YYm= NVy3XZF2OzBizszN M4TKe2ROW09? M1fKOolv\HWlZYOgZZV1d3CqYXf5 MWSyOlg5PTZyOB?=

... Click to View More Cell Line Experimental Data

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

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€

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:


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  • 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.

* 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
in solvent
Synonyms Erismodegib
Smiles CC1CN(CC(C)O1)C2=CC=C(NC(=O)C3=C(C)C(=CC=C3)C4=CC=C(OC(F)(F)F)C=C4)C=N2

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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