SB525334

製品コード：S1476 純度：99.99%

SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.

CAS No. 356559-20-1

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
10mg	JPY 35500	国内在庫あり
100mg	JPY 145500	国内在庫あり
1g	JPY 295500	国内在庫あり

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（101）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

SB525334関連製品

関連ターゲット	ALK1 ALK2 ALK3 ALK4 TGFβRI/ALK5 ALK6 TGFβRII TGF-β Smad3 Smad4 Smad5 ALK7	もっと見る
関連製品	SB431542 LDN-193189 Galunisertib (LY2157299) LY2109761 LDN-193189 2HCl SIS3 HCl RepSox (E-616452) LY364947 DMH1 SB505124 GW788388 A-83-01 SD-208 K02288 Vactosertib (TEW-7197) SIS3 Kartogenin ITD-1 LDN-212854 LY 3200882 ML347 TP0427736 HCl SRI-011381 (C381) LDN-214117 Hesperetin Alantolactone TGFβRI-IN-3 Anti-human/mouse TGF-β-InVivo	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library	もっと見る

シグナル伝達経路

TGF-beta/Smadシグナル伝達経路

TGF-beta/Smad阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
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
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 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
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
Sf9	Function assay			Inhibition of human recombinant GST-fused ALK5 expressed in Sf9 cells, IC50 = 0.162 μM.	20472445
ELT-3	Function Assay	0.5/1.0/2.0 μM	1 h	inhibits TGF-β signaling in leiomyomas	17505012
AsPC1	Cell Viability Assay	0-10 μM	72 h	efficiently reduces the viability with	22399597
PASMCs	Function Assay	1 μM	15 min	inhibits TGF-β1-mediated proliferation of familial iPAH PASMCs at an IC50 of 295 nmol/L	19116361
rhPOSTN	Apoptosis Assay	0.5 μM	48 h	significantly decreases the number of apoptotic cells	24129188
HUVECs	Function Assay	10 μM	24/48/72 h	leads to a disruption of the HUVEC monolayer after 72 hr	23968981
HUVECs	Function Assay	10 μM	72 h	blocks signaling	23968981
HUVECs	Function Assay	10 μM	72 h	reduces the phosphorylation of smad2	23968981
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
MiaPaCa2	Cell Viability Assay	0-10 μM	72 h	efficiently reduces the viability with	22399597
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生物活性

製品説明

SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.

Targets

TGFβR1(ALK5) ^[1]
(Cell-free assay)

14.3 nM

In Vitro
In vitro	SB 525334 shows no inhibition in the enzymes ALK2, 3, and 6, with IC50 values > 10 μM. SB 525334 blocks phosphorylation induced by TGF-β1 and nuclear translocation of Smad2/3 in renal proximal tubule cells. SB 525334 also inhibits the increased mRNA expression levels of plasminogen activator inhibitor-1 (PAI-1) and procollagen α1(I) induced by TGF-β1 in A498 renal epithelial carcinoma cells at 1 μM). ^[1] SB 525334 (1 μM) attenuates the heightened sensitivity to TGF-β1 exhibited by pulmonary artery smooth muscle cells (PASMCs) from patients with familial forms of idiopathic pulmonary arterial hypertension (PAH). ^[2]
Kinase Assay	Kinase assay to determine the potency and selectivity of SB 525334
Kinase Assay	In order to determine the potency of SB 525334, purified GST-tagged kinase domain of ALK5 is incubated with purified GST-tagged full-length Smad3 in the presence of ³³P-γATP and different concentrations of SB 525334. The readout is radioactively labeled Smad3.To determine the selectivity of SB 525334, purified GST-tagged kinase domain of ALK2 and ALK4 are incubated with GST-tagged full-length Smad1 and Smad3, respectively, in the presence of different concentrations of SB 525334. IC50 values are calculated.
細胞実験	細胞株	Human renal proximal tubule epithelial (RPTE) cells
	濃度	1 μM
	反応時間	1 hour
	実験の流れ	RPTE cells are seeded on microscope slides. The following day, the cells are starved for 24 hours to dosing by removal of the serum and epidermal growth factor. Cells are treated with either 10 ng/mL TGF-β1, 1 μM SB 525334, or a combination of both. Slides are pretreated with SB 525334 or starve media for 3 hours prior to a 1-hour incubation at 37 °C with TGF-β1 or starve media. The cells are then fixed and permeabilized. The slides are blocked with BSA, incubated with a mouse anti-Smad2/3 primary antibody followed by an anti-mouse IgG secondary antibody. The slides are then viewed in a confocal microscope and nuclear signal intensity is analyzed.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Fibronectin / E-cadherin / Hif-1α		29127306
	Immunofluorescence	E-cadherin / Vimentin		27471572

In Vivo
In Vivo	SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. Furthermore, PAN-induced proteinuria is significantly inhibited by SB 525334 (10 mg/kg/day). ^[1] SB 525334 may also be efficacious in mesenchymal tumors. SB 525334 (10 mg/kg/day) significantly decreases uterine mesenchymal tumor incidence, multiplicity, and size in Eker rats. ^[3] SB 525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. This is revealed by a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used to induce PAH) after treatment with SB 525334 (3 or 30 mg/kg). ^[2] In a induced pulmonary fibrosis mice model, SB 525334 (10 mg/kg or 30 mg/kg) attenuates the histopathological alterations in the lung, and significantly decreased mRNA expression of Type I and III procollagen and fibronectin. SB 525334 also attenuates Smad2/3 nuclear translocation, myofibroblast proliferation, deposition of Type I collagen, and decreases CTGF-expressing cells. ^[4]
動物実験	動物モデル	induced pulmonary fibrosis in female Eker rats
	投与量	Estimated dose of 10 mg/kg/day
	投与経路	Oral (in drinking water)

参考
[1] Grygielko ET, et al. J Pharmacol Exp Ther, 2005, 313(3), 943-951. [2] Thomas M, et al. Am J Pathol, 2009, 174(2), 380-389. [3] Laping NJ, et al. Clin Cancer Res, 2007, 13(10), 3087-3899. [4] Higashiyama H, et al. Exp Mol Pathol, 2007, 83(1), 39-46. + 展開

参考

[4] Higashiyama H, et al. Exp Mol Pathol, 2007, 83(1), 39-46.

+ 展開

化学情報

分子量	343.42	化学式	C₂₁H₂₁N₅
CAS No.	356559-20-1	SDF	Download SB525334 SDFをダウンロードする
Smiles	CC1=NC(=CC=C1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=NC=CN=C4C=C3
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 : 69 mg/mL ( (200.92 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 : 69 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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よくある質問（FAQ）

質問1:
I want to know the feasibility of using the compound via oral gavage in rodents (dosing, frequency, formulation…)?

回答
Our S1476 can be used for oral gavage in rodents, and the vehicle we suggest is: 30% Propylene glycol, 5% Tween 80, 65% D5W (dextrose(5%)in water) at 20mg/ml maximum. Based on the following reference they administrated it at an estimated dose of 10 mg/kg/day in rat for 2 months: http://clincancerres.aacrjournals.org/content/13/10/3087.long

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