Home TGF-beta/Smad TGF-beta/Smad inhibitor LDN-193189 2HCl For research use only.

LDN-193189 2HCl

Synonyms: DM-3189 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.

LDN-193189 2HCl Chemical Structure

LDN-193189 2HCl Chemical Structure

CAS No. 1435934-00-1

Purity & Quality Control

Products often used together with LDN-193189 2HCl

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 Related Products

Signaling Pathway

TGF-beta/Smad Signaling Pathways

TGF-beta/Smad Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
PC3 Function assay 500 nM LDN-193189 repressed activation of Smad1/5/8, and also repressed P-Smad3 levels 22452883
C2C12 Function assay 0.5 μM 1 day LDN-193189 promotes myogenesis 25368322
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Features 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 ALK2R206H or ALK2Q207D 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
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.
Experimental Result Images Methods Biomarkers Images PMID
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]
Animal Research Animal Models Ad.Cre on P7 is injected into conditional caALK2–transgenic and wild-type mice.
Dosages ≤3 mg/kg
Administration Administered via i.p.

Chemical Information & Solubility

Molecular Weight 479.4 Formula

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
Storage (From the date of receipt)

In vitro
Batch:

Water : 24 mg/mL

DMSO : 12 mg/mL ( (25.03 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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