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Sonidegib Hedgehog/Smoothened antagonist

Name: Sonidegib
SKU: S2151
Availability: InStock
Rating: 5 (72 reviews)

Cat.No.S2151

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.

Chemical Structure

Molecular Weight: 485.5

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.90%

99.90

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Cell Culture, Treatment & Working Concentration

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
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	485.5	Formula	C₂₆H₂₆F₃N₃O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	956697-53-3	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	NVP-LDE225, Erismodegib			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

Solubility

In vitro
Batch:

DMSO : 97 mg/mL (199.79 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	Smo (mouse) ^[1] (Cell-free assay) 1.3 nM Smo (human) ^[1] (Cell-free assay) 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]
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 pK_a 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]
References	[1] http://pubs.acs.org/doi/full/10.1021/ml1000307 [2] https://pubmed.ncbi.nlm.nih.gov/22042473/ [3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3332451/

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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