LDN-193189 2HCl

LDN-193189 (DM3189) 2HCl 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.

CAS No. 1435934-00-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 41500	国内在庫あり
5mg	JPY 29500	国内在庫あり
50mg	JPY 127000	国内在庫あり
1g	JPY 598500	国内在庫なし(納期7~10日)

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文献中Selleckの製品使用例（93）

製品安全説明書

現在のバッチを見る：純度： 99.47%

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LDN-193189 2HClと併用されることが多い化合物

SB431542

LDN 193189 2HCL and SB43154 when used together promote scalable generation of hPSC-derived nociceptors.

Chambers SM, et al. Nat Biotechnol. 2012 Jul; 30(7): 715–720.

K02288

LDN-193189 2HCl and K02288 treatment significantly compromises trophoblast trans-differentiation induced by Cited1 overexpression in E14T ESCs.

Xu Y, et al. Cell Death Dis. 2018 Sep; 9(9): 924.

IWP-2

LDN-193189 2HCl and IWP2 are used to verify the function of WNT and BMP signaling, during 3D culture of human embryos from E6–14.

Ai Z, et al. Cell Res. 2023 Jul 17.

ML347

LDN-193189 2HCl and ML347 target the BMP receptors ALK2/3/6 and inhibit SMAD1/5/8 phosphorylation without affecting the type I TGF-beta receptor ALK5 or the SMAD2/3 pathway.

Taylor KR, et al. Cancer Res. 2014 Sep 1; 74(17): 4565–4570.

SB505124

LDN-193189 2HCl completely abolishes BMP12-triggered phosphorylation of Smad1/5/8, but not by the ALK4/5 and 7 inhibitor SB-505124.

Shen H, et al. PLoS One. 2013 Oct 14;8(10):e77613.

LDN-193189 2HCl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
EOC216	Cell viability assay	0.1, 1, 2, 5, 10 μM	1, 3, 5, 7, 9 days	exhibited a dose dependent LDN-induced decrease in viability	25227893
C2C12	Function assay	0.5 μM	1 day	LDN-193189 promotes myogenesis	25368322
PC3	Function assay	500 nM		LDN-193189 repressed activation of Smad1/5/8, and also repressed P-Smad3 levels	22452883
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
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 cells	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
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生物活性

製品説明

LDN-193189 (DM3189) 2HCl 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.

特性

Selective BMP type I receptor inhibitor.

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.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	pSmad Smad / ID1 / PARP / Cleaved PARP		19029982

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. [6] Sanvitale CE, et al. PLoS One. 2013 Apr 30;8(4):e62721. + 展開

参考

+ 展開

化学情報

分子量	479.4	化学式	C₂₅H₂₄Cl₂N₆
CAS No.	1435934-00-1	SDF	--
Smiles	C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC6=CC=CC=C56)N=C3.Cl.Cl
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:

Water : 88 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。)

Ethanol : 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):