LDN-193189

LDN-193189 (DM3189) is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. For animal testing, the water-soluble S7507 LDN-193189 2HCl is recommended.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!

CAS No. 1062368-24-4

サイズ	価格(税別)	在庫状況
2mg	JPY 22000	国内在庫あり
5mg	JPY 37000	国内在庫あり
25mg	JPY 89500	国内在庫あり
1g	JPY 598500	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

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製品安全説明書

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LDN-193189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 Galunisertib (LY2157299) LY2109761 SB525334 LDN-193189 2HCl SIS3 HCl RepSox (E-616452) LY364947 Pirfenidone 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
Bx-PC3	Growth Inhibition Assay	5-500 nM	48 h	inhibits cell growth in a dose-dependent manner	23969729
MIA PaCa-2	Growth Inhibition Assay	5-500 nM	48 h	inhibits cell growth in a dose-dependent manner	23969729
PANC-1	Growth Inhibition Assay	5-500 nM	48 h	inhibits cell growth in a dose-dependent manner	23969729
hBMSCs	Function Assay	0.2 μM	7 d	abolishes the silibinin-promoted ALP activity partly	24076187
EOC219	Growth Inhibition Assay	2/5 μM	48 h	decreases the percentage of cells in S phas	25227893
OVCA429	Growth Inhibition Assay	2/5 μM	48 h	decreases the percentage of cells in S phas	25227893
SKOV3	Growth Inhibition Assay	2/5 μM	48 h	decreases the percentage of cells in S phas	25227893
OVAC429	Growth Inhibition Assay	2/5 μM	48 h	decreases the percentage of cells in S phas	25227893
EOC216	Growth Inhibition Assay	0.1-10 μM	2-10 d	induce cell death in a dose-dependent manner	25227893
PC3	Function Assay	500 nM	2 h	represses activation of Smad1/5/8 and P-Smad3 levels	22452883
LNCaP	Function Assay	0–500 nM	2 h	reverses rapamycin-induced cell death	22452883
EOC	Function Assay	10-1000 nM	72 h	reduces the phosphorylated BMP R-Smad1/5/8	22249415
HaCaT	Function Assay	0.001-10 μM	2 h	inhibits BMP2-induced phosphorylation of Smad1/5/8 with an IC50 of ~0.005 μM	21740966
HaCaT	Function Assay	0.001-10 μM	2 h	inhibits the ability of ALK2 to phosphorylate GST-Smad1 with an IC50 of 45 nM	21740966
HaCaT	Function Assay	0.001-10 μM	2 h	inhibits the ability of ALK3 to phosphorylate Smad1 with an IC50 of 100 nM	21740966
HaCaT	Function Assay	0.001-10 μM	2 h	inhibits ALK4 and ALK5 with IC50 values of 0.3 μM and 0.5 μM respectively	21740966
BEAS-2B	Growth Inhibition Assay	0.5-16 μM		inhibits cell growth in a dose-dependent manner	24778011
A549	Growth Inhibition Assay	0.5-16 μM		inhibits cell growth in a dose-dependent manner	24778011
C2C12	Function assay	0.1 uM		Inhibition of ALK5 in mouse C2C12 cells assessed as decrease in TGFbeta1-induced Smad1/5 phosphorylation at 0.1 uM by Western blot method	28103025
C2C12	Function assay		30 mins	Inhibition of BMP6-induced ALK2 transcriptional activity in mouse C2C12 cells expressing BRE-Luc after 30 mins by luciferase reporter gene assay, EC50 = 0.014 μM.	30227946
C2C12	Kinase Assay			inhibits the kinase activity of ALK4 and ActRIIA with IC50 values of 101 and 210 nm, respectively	25368322
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
fibroblast cell	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
KB-3-1	Function assay			P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	31515284
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生物活性

製品説明

LDN-193189 (DM3189) is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. For animal testing, the water-soluble S7507 LDN-193189 2HCl is recommended.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!

Targets

ALK1 ^[5] (Cell-free assay)	ALK2 ^[5] (Cell-free assay)	ALK3 ^[5] (Cell-free assay)	ALK6 ^[5] (Cell-free assay)
0.8 nM	0.8 nM	5.3 nM	16.7 nM

In Vitro
In vitro	LDN193189 potently inhibits BMP4-mediated Smad1, Smad5 and Smad8 activation with IC50 of 5 nM, and efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively. Furthermore, LDN193189 also shows the inhibitory effect on the transcriptional activity induced by either constitutively active ALK2^R206H or ALK2^Q207D mutant proteins. ^[1] A recent study shows that LDN-193189 blocks the production of reactive oxygen species induced by oxidized LDL during atherogenesis in human aortic endothelial cells. ^[4]
Kinase Assay	Alkaline phosphatase activity
Kinase Assay	C2C12 cells are seeded into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. The wells are treated in quadruplicate with BMP ligands and LDN-193189 or vehicle. The cells are collected after 6 days in culture in 50 μL Tris-buffered saline and 1% Triton X-100. The lysates are added to p-nitro-phenylphosphate reagent in 96-well plates for 1 hours and then evaluated alkaline phosphatase activity (absorbance at 405 nm). Cell viability and quantity are measured by Cell Titer Aqueous One (absorbance at 490 nm), using replicate wells treated identically to those used for alkaline phosphatase measurements.
細胞実験	細胞株	PASMCs
	濃度	5 nM
	反応時間	12 h
	実験の流れ	Cells were treated with various concnetrations of LDN-193189.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pSMAD1 / pSMAD5 / pSMAD8 / SMAD1 / SMAD5 / SMAD8 / ID1 / SMAD4 / PARP / Cleaved PARP		31098401
	Immunofluorescence	Tbx18 / Hcn4		30906456
	Growth inhibition assay	Cell viability		31098401

In Vivo
In Vivo	In conditional caALK2-transgenic mice with Ad.Cre on on postnatal day 7 (P7), LDN-193189 (3 mg/kg i.p) leads to mild calcifications surrounding the left tibia and fibula first visible at P13, and prevents radiographic lesions at P15 without causing weight loss or growth retardation, spontaneous fractures, decreased bone density or behavioral abnormalities. ^[1] LDN193189 dorsalizes zebrafish embryos by inhibiting signaling pathways induced by bone morphogenetic protein (BMP)6 without effect on vascular development. ^[2] In PCa-118b tumor-bearing mice, LDN-193189 treatment attenuates tumor growth and reduces bone formation in the tumors. ^[3] In LDL receptor-deficient (LDLR-/-) mice, LDN-193189 potently inhibits development of atheroma. Moreover, LDN-193189 also exhibits the inhibitory effects on associated vascular inflammation, osteogenic activity, and calcification. ^[4]
動物実験	動物モデル	Ad.Cre on P7 is injected into conditional caALK2–transgenic and wild-type mice.
	投与量	≤3 mg/kg
	投与経路	Administered via i.p.

参考
[1] Yu PB, et al. Nat Med, 2008, 14(12), 1363-1369. [2] Cannon JE, et al. Br J Pharmacol, 2010, 161(1), 140-149. [3] Lee YC, et al. Cancer Res, 2011, 71(15), 5194-5203. [4] Derwall M, et al. Arterioscler Thromb Vasc Biol, 2012, 32(3), 613-622. [5] Caroline E Sanvitale, et al. PLoS One. 2013 Apr 30;8(4):e62721. + 展開

参考

+ 展開

化学情報

分子量	406.48	化学式	C₂₅H₂₂N₆
CAS No.	1062368-24-4	SDF	Download LDN-193189 SDFをダウンロードする
Smiles	C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC6=CC=CC=C56)N=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:

0.01M HCl : 2.5 mg/mL

DMSO : Insoluble ( 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。)

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。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):