Sonidegib

別名：NVP-LDE225, Erismodegib

製品コード：S2151 純度：99.90%

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.

CAS No. 956697-53-3

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 70500	国内在庫あり
100mg	JPY 145500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（65）

製品安全説明書

現在のバッチを見る：純度： 99.90%

99.90

Sonidegib関連製品

関連ターゲット	Hedgehog Smoothened GLI	もっと見る
関連製品	Cyclopamine GANT61 SAG (Smoothened Agonist) HCl Purmorphamine SANT-1 SAG (Smoothened Agonist) BMS-833923 HPI-4 (Ciliobrevin A) Taladegib (LY2940680) PF-5274857 Jervine Ciliobrevin D MK-4101 JK184	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Stem Cell Signaling Compound Library GPCR Compound Library Stem Cell Differentiation Compound Library	もっと見る

シグナル伝達経路

Hedgehog/Smoothenedシグナル伝達経路

Hedgehog/Smoothened阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
UACC 257	Function assay	10 μM		inhibits Hedgehog-GLI pathway	23935925
LOX IMVI	Function assay	10 μM		inhibits Hedgehog-GLI pathway	23935925
Glioblastoma initiating cells	Function assay	~10 μM		Inhibits Motility, Invasion, and Migration	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		downregulates the SHH signaling pathway	23482671
Glioblastoma initiating cells	Cytoxicity assay	~10 μM		induces apoptosis	23482671
Glioblastoma initiating cells	Function assay	~10 μM		inhibits neurosphere formation	23482671
Glioblastoma initiating cells	Cytoxicity assay	~10 μM		Inhibits Cell Viability	23482671
OS18	Growth inhibitory assay	~5 μM		reduces the proliferation	23243595
OS5	Growth inhibitory assay	~5 μM		reduces the proliferation	23243595
HeyA8MDR	Cytoxicity assay	~10 μM		IC50=8 μM	22553355
HeyA8	Cytoxicity assay	~10 μM		IC50=18 μM	22553355
SKOV3TRip2	Cytoxicity assay	~10 μM		IC50=12 μM	22553355
SKOV3ip1	Cytoxicity assay	~10 μM		IC50=24 μM	22553355
A2780cp20	Cytoxicity assay	~10 μM		IC50=7.5 μM	22553355
A2780ip2	Cytoxicity assay	~10 μM		IC50=12 μM	22553355
LOX IMVI	Function assay	10 μM		induces G1 cell cycle arrest	23935925
UACC 257	Function assay	10 μM		induces G1 cell cycle arrest	23935925
LOX IMVI	Cytoxicity assay	10 μM		decreases tumor cell viability	23935925
UACC 257	Cytoxicity assay	10 μM		decreases tumor cell viability	23935925
LOX IMVI	Apoptosis assay	10 μM		induces apoptosis	23935925
UACC 257	Apoptosis assay	10 μM		induces apoptosis	23935925
ACHN	Growth inhibitory assay	~5 μM		IC50=2-3 μM	25093491
769-P	Growth inhibitory assay	~5 μM		IC50=2-3 μM	25093491
786-O	Growth inhibitory assay	~5 μM		IC50=2-3 μM	25093491
786-O SuR	Growth inhibitory assay	~5 μM		IC50=2-3 μM	25093491
SP53	Function assay	30 μM		inhibits cell adhesion and migration	26885608
SP53	Function assay	30 μM		inhibits the VLA4-mediated FAK signaling pathway	26885608
HS5	Function assay	30 μM		inhibits cell adhesion and migration	26885608
HS27a	Function assay	30 μM		inhibits cell adhesion and migration	26885608
SP53	Cytoxicity assay	30 μM		induces autophagy	26885608
Jeko	Cytoxicity assay	30 μM		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		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 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			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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生物活性

製品説明

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]
細胞実験	細胞株	TM3Hh12 cells
	濃度	~10 μM
	反応時間	30 minutes
	実験の流れ	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
実験結果図	Methods	Biomarkers	結果図	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 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]
動物実験	動物モデル	Orthotopic Ptch^+/-p53^-/- medulloblastoma allograft model in athymic nude mice
	投与量	40 mg/kg/day
	投与経路	Administered via p.o. or b.i.d

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Pan SF, et al. ACS Med. Chem. Lett., 2010, 1 (3), 130–134. [2] Fendrich V, et al. Ann Surg, 2011, 254(5), 818-23. [3] Tauchi T, et al. Arthritis Res Ther, 2012, 14(Suppl 1), O43.

参考

化学情報

分子量	485.5	化学式	C₂₆H₂₆F₃N₃O₃
CAS No.	956697-53-3	SDF	Download Sonidegib SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 97 mg/mL ( (199.79 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 16 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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