Home Stem Cells & Wnt Hedgehog/Smoothened antagonist Sonidegib For research use only.

Sonidegib

Synonyms: NVP-LDE225, Erismodegib

Sonidegib 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.

Sonidegib Chemical Structure

Sonidegib Chemical Structure

CAS No. 956697-53-3

Purity & Quality Control

Sonidegib Related Products

Signaling Pathway

Hedgehog/Smoothened Signaling Pathways

Hedgehog/Smoothened Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780ip2 Cytoxicity assay ~10 μM IC50=12 μM 22553355
A2780cp20 Cytoxicity assay ~10 μM IC50=7.5 μM 22553355
SKOV3ip1 Cytoxicity assay ~10 μM IC50=24 μM 22553355
SKOV3TRip2 Cytoxicity assay ~10 μM IC50=12 μM 22553355
HeyA8 Cytoxicity assay ~10 μM IC50=18 μM 22553355
HeyA8MDR Cytoxicity assay ~10 μM IC50=8 μM 22553355
OS5 Growth inhibitory assay ~5 μM reduces the proliferation 23243595
OS18 Growth inhibitory assay ~5 μM reduces the proliferation 23243595
Glioblastoma initiating cells Cytoxicity assay ~10 μM Inhibits Cell Viability 23482671
Glioblastoma initiating cells Function assay ~10 μM inhibits neurosphere formation 23482671
Glioblastoma initiating cells Cytoxicity assay ~10 μM induces apoptosis 23482671
Glioblastoma initiating cells Function assay ~10 μM downregulates the SHH signaling pathway 23482671
Glioblastoma initiating cells Function assay ~10 μM Inhibits the Expression of Genes Involved in Maintaining Pluripotency 23482671
Glioblastoma initiating cells Function assay ~10 μM Inhibits Motility, Invasion, and Migration 23482671
LOX IMVI Function assay 10 μM DMSO inhibits Hedgehog-GLI pathway 23935925
UACC 257 Function assay 10 μM DMSO inhibits Hedgehog-GLI pathway 23935925
LOX IMVI Function assay 10 μM DMSO induces G1 cell cycle arrest 23935925
UACC 257 Function assay 10 μM DMSO induces G1 cell cycle arrest 23935925
LOX IMVI Cytoxicity assay 10 μM DMSO decreases tumor cell viability 23935925
UACC 257 Cytoxicity assay 10 μM DMSO decreases tumor cell viability 23935925
LOX IMVI Apoptosis assay 10 μM DMSO induces apoptosis 23935925
UACC 257 Apoptosis assay 10 μM DMSO induces apoptosis 23935925
ACHN Growth inhibitory assay ~5 μM DMSO IC50=2-3 μM 25093491
769-P Growth inhibitory assay ~5 μM DMSO IC50=2-3 μM 25093491
786-O Growth inhibitory assay ~5 μM DMSO IC50=2-3 μM 25093491
786-O SuR Growth inhibitory assay ~5 μM DMSO IC50=2-3 μM 25093491
SP53 Function assay 30 μM DMSO inhibits cell adhesion and migration 26885608
SP53 Function assay 30 μM DMSO inhibits the VLA4-mediated FAK signaling pathway 26885608
HS5 Function assay 30 μM DMSO inhibits cell adhesion and migration 26885608
HS27a Function assay 30 μM DMSO inhibits cell adhesion and migration 26885608
SP53 Cytoxicity assay 30 μM DMSO induces autophagy 26885608
Jeko Cytoxicity assay 30 μM DMSO induces autophagy 26885608
U2OS Function assay 2 hrs Displacement of [3H]cyclopamine from wild type Smo expressed in U2OS cells after 2 hrs by scintillation counting, Ki = 0.006 μM. 23063522
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells expressing wild type Smo assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0044 μM. 27810591
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells harboring Smo D477H mutant assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0227 μM. 27810591
NIH/3T3 Function assay 24 hrs Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells measured after 24 hrs by Gli-dual luciferase reporter gene assay, IC50 = 0.006 μM. 27810591
TM3 Function assay 48 hrs Inhibition of Hh signaling pathway in mouse TM3 cells assessed as downregulation of Gli1 gene expression after 48 hrs by luciferase reporter gene assay, EC50 = 0.0012 μM. 26976215
NIH3T3 Function assay 48 hrs Inhibition of SHH signaling pathway in mouse NIH3T3 cells measured after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0055 μM. 24176396
NIH3T3 Function assay 48 hrs Inhibition of Sonic-induced hedgehog signalling in mouse NIH3T3 cells after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0055 μM. 26820554
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway expressed in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Gli-2 accumulation at tip of primary cilia by DAPI staining based confocal microscopic analysis 27810591
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Smo-EGFP ciliary translocation by DAPI staining based confocal microscopic analysis 27810591
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
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Biological Activity

Description Sonidegib 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
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 Research 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
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-p130CAS / p130CAS / p-FAK / FAK / p-Paxillin / Paxillin pp70S6K / P70s6k Gli-1 / Gli-2 / p-Akt / Akt Bcl2 / c-myc / Cyclin D1 / pERK / ERK / pJNK / JNK / Caspase 3 / Cleaved caspase 3 25093491
Immunofluorescence GLI1 22821765
In Vivo
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]
Animal Research Animal Models Orthotopic Ptch+/-p53-/- medulloblastoma allograft model in athymic nude mice
Dosages 40 mg/kg/day
Administration Administered via p.o. or b.i.d
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02358161 Completed
Pancreatic Cancer
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Novartis|Celgene Corporation
 September 2015 Phase 1|Phase 2
NCT02254551 Terminated
Multiple Myeloma
SCRI Development Innovations LLC|Novartis
 January 2015 Phase 2
NCT02138929 Completed
Esophageal Cancer
M.D. Anderson Cancer Center|Novartis|National Cancer Institute (NCI)
 November 10 2014 Phase 1
NCT02195973 Completed
Recurrent Ovarian Cancer
University of Alabama at Birmingham|Novartis Pharmaceuticals
 September 2014 Phase 1
NCT02027376 Completed
Advanced Breast Cancer
Spanish Breast Cancer Research Group|Novartis
 May 2014 Phase 1
NCT02111187 Completed
Prostate Cancer
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 April 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 485.5 Formula

C26H26F3N3O3
CAS No. 956697-53-3 SDF Download Sonidegib SDF
Smiles CC1CN(CC(O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 97 mg/mL ( (199.79 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble


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In vivo
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Tech Support

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