LDN-193189

For research use only.

Catalog No.S2618 Synonyms: DM3189

153 publications

LDN-193189 Chemical Structure

CAS No. 1062368-24-4

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.

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Selleck's LDN-193189 has been cited by 153 publications

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Choose Selective TGF-beta/Smad Inhibitors

Biological Activity

Description 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.
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

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
C2C12 NEXseVlMcW6jc3WgRZN{[Xl? NUX0dHZDcW6qaXLpeJMhfGinIHvpcoF{\SCjY4Tpeol1gSCxZjDBUGs1KGGwZDDBZ5RTUUmDIIfpeIghUUN3MNMgeoFtfWW|IH;mJFExOSCjbnSgNlExKG6vLDDy[ZNx\WO2aY\lcJk> MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTN4OEOyNkc,OjV|NkizNlI9N2F-
EOC216 M3zIR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2KwUlAvOS1zMDFOwG0> MorCNk0yOCCm M3HCfGROW09? M3;1SIlv\HWlZTDj[YxtKGSnYYToJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NV;QVJM3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNlc5QTNpPkK1NlI4QDl|PD;hQi=>
OVAC429 MkjMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorONk82KM7:TR?= NUnKV3h1PDhiaB?= M17sWGROW09? NF;IW4Vl\WO{ZXHz[ZMhfGinIIDldoNmdnSjZ3Wgc4Yh[2WubIOgbY4hWyCyaHHz MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ{N{i5N{c,OjV{Mke4PVM9N2F-
SKOV3 NH7yNo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDCfIplOi93IN88US=> NWnNW|k2PDhiaB?= MoGzSG1UVw>? NV;OWIp4\GWlcnXhd4V{KHSqZTDw[ZJk\W62YXflJI9nKGOnbHzzJIlvKFNicHjhdy=> M1jCXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkK3PFk{Lz5{NUKyO|g6OzxxYU6=
OVCA429 M{PaWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3ryZ|IwPSEQvF2= MW[0PEBp MlXGSG1UVw>? MXjk[YNz\WG|ZYOgeIhmKHCncnPlcpRi\2Vib3[gZ4VtdHNiaX6gV{BxcGG| M1fsR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkK3PFk{Lz5{NUKyO|g6OzxxYU6=
EOC219 M3HESmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXOyM|Uh|ryP MkDwOFghcA>? MnHFSG1UVw>? NEnUWGNl\WO{ZXHz[ZMhfGinIIDldoNmdnSjZ3Wgc4Yh[2WubIOgbY4hWyCyaHHz M3vLZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkK3PFk{Lz5{NUKyO|g6OzxxYU6=
A549 Mln3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXqwMlUuOTZizszN NFu4dFZFVVOR M4LieolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NECxbVI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PFAyOSd-MkS3O|gxOTF:L3G+
BEAS-2B  M17VdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU[wMlUuOTZizszN M{TobGROW09? MVnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NXLTfoNTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3O|gxOTFpPkK0O|c5ODFzPD;hQi=>
hBMSCs MYHGeY5kfGmxbjDBd5NigQ>? NHW1emgxNjMEoN88US=> MmHxO{Bl M13hN4Fjd2yrc3jld{B1cGVic3nsbYJqdmmwLYDyc41wfGWmIFHMVEBi[3Srdnn0feKheGG{dHz5 M3\D[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEe2NVg4Lz5{NEC3OlE5PzxxYU6=
PANC-1 NG\kPZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWm1MVUxOCCwTR?= NHPZR4w1QCCq NGThXVVqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MlLsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7Nkm3NlkoRjJ|OU[5O|I6RC:jPh?=
MIA PaCa-2 MnHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEL1bI02NTVyMDDuUS=> MYK0PEBp M3TjeYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NFK1cWQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2PVczQSd-MkO5Olk4Ojl:L3G+
Bx-PC3 NVnjcYo2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUGzW5VDPS13MECgcm0> NIrrT3c1QCCq NFqxdZJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NUnFV5NrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5Olk4OjlpPkKzPVY6PzJ7PD;hQi=>
PC3  M3znbmZ2dmO2aX;uJGF{e2G7 MmTtOVAxKG6P NUfvNVRFOiCq NHznWnFz\XC{ZYPz[ZMh[WO2aY\heIlwdiCxZjDTcYFlOS93L{igZY5lKFBvU33h[FMhdGW4ZXzz NYCzSGlyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0OVI5QDNpPkKyOFUzQDh|PD;hQi=>
LNCaP Mn\mSpVv[3Srb36gRZN{[Xl? MmGyNQKBmzVyMDDuUS=> MWKyJIg> MmXBdoV3\XK|ZYOgdoFx[W27Y3nuMYlv\HWlZXSgZ4VtdCCmZXH0bC=> NUn2UYpYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0OVI5QDNpPkKyOFUzQDh|PD;hQi=>
EOC MVzGeY5kfGmxbjDBd5NigQ>? Mn;YNVAuOTByMDDuUS=> NFK1Rnk4OiCq MmX4doVlfWOnczD0bIUheGixc4Doc5J6dGG2ZXSgRm1RKFJvU33h[FEwPS96wrC= NWPFOINCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOFk1OTVpPkKyNlQ6PDF3PD;hQi=>
HaCaT  M4fYe2Z2dmO2aX;uJGF{e2G7 NE\jUY4xNjByMT2xNEDPxE1? MWCyJIg> MWjpcohq[mm2czDCUXAzNWmwZIXj[YQheGixc4Doc5J6dGG2aX;uJI9nKFOvYXSxM|UwQCC5aYToJIFvKEmFNUFCpI9nKH5yLkCwOeKh|ryP NEfu[Gc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUe0NFk3Pid-MkG3OFA6PjZ:L3G+
HaCaT  MVPGeY5kfGmxbjDBd5NigQ>? M2HUNFAvODBzLUGwJO69VQ>? M1fB[VIhcA>? MVTpcohq[mm2czD0bIUh[WKrbHn0fUBw\iCDTFuyJJRwKHCqb4PwbI9zgWyjdHWgS3NVNVOvYXSxxsB4cXSqIHHuJGlEPTEEoH;mJFQ2yqCwTR?= NEnaeoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUe0NFk3Pid-MkG3OFA6PjZ:L3G+
HaCaT  Ml30SpVv[3Srb36gRZN{[Xl? M{DMbFAvODBzLUGwJO69VQ>? M4PQVFIhcA>? NFLtOJRqdmirYnn0d{B1cGViYXLpcIl1gSCxZjDBUGs{KHSxIIDoc5NxcG:{eXzheIUhW22jZEJCpJdqfGhiYX6gTWM2OMLib3[gNVAxKG6P NGDac|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUe0NFk3Pid-MkG3OFA6PjZ:L3G+
HaCaT  NGPtd|JHfW6ldHnvckBCe3OjeR?= MWqwMlAxOS1zMDFOwG0> NXHpfI53OiCq MXnpcohq[mm2czDBUGs1KGGwZDDBUGs2KHerdHigTWM2OMLidnHseYV{KG:oIECuN:Kh|ryPIHHu[EAxNjYEoN88UUBz\XOyZXP0bZZmdHl? NYjHWY1bRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3OFA6PjZpPkKxO|QxQTZ4PD;hQi=>
C2C12 MmTCSpVv[3Srb36gZZN{[Xl? NYnpWol1OzBibXnudy=> M2XXe2lvcGmkaYTpc44hd2ZiQl3QOk1qdmS3Y3XkJGFNUzJidILhcpNkemmydHnvcoFtKGGldHn2bZR6KGmwIH3veZNmKEN{Q{GyJINmdGy|IHX4dJJme3OrbnegRnJGNUy3YzDh[pRmeiB|MDDtbY5{KGK7IHz1Z4ln\XKjc3WgdoVxd3K2ZYKg[4Vv\SCjc4PhfUwhTUN3MDC9JFAvODF2IN88UU4> MlXWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB{Mke5OFYoRjNyMkK3PVQ3RC:jPh?=
BT-12 M4HMbpFJXFNiYYPzZZk> M1z5fZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?= NEjhTYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
fibroblast cell MojBdWhVWyCjc4PhfS=> M1zqOZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiClb370do9tKEiqIIfpcIQhfHmyZTDmbYJzd2KuYYP0JINmdGy| NVHEPFFzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh30 MoHQdWhVWyCjc4PhfS=> M3PHS5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEOwJINmdGy| MnuyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
KB-3-1 MXXGeY5kfGmxbjDhd5NigQ>? MVXQMYdtgWOxcILveIVqdiC|dXLzeJJifGW|IHnk[Y51cW[rZXSgbY4hU0JvMz2xJIFl\W6xY3HyZ4lvd22jIHPlcIwhdGmwZTygdWhVWyC2aHXyZZBmfXSrYzDsbYJz[XK7IIPjdoVmdg>? NV7XPWY1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{G1NVUzQDRpPkOxOVE2Ojh2PD;hQi=>
C2C12 MnroSpVv[3Srb36gZZN{[Xl? NUDKTZc5OC5zIIXN NULFO|RKUW6qaXLpeIlwdiCxZjDBUGs2KGmwIH3veZNmKEN{Q{GyJINmdGy|IHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKFSJRnLleIEyNWmwZIXj[YQhW22jZEGvOUBxcG:|cHjvdplt[XSrb36gZZQhOC5zIIXNJIJ6KFenc4Tldo4h[myxdDDt[ZRpd2R? NEDWNnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEGwN|AzPSd-MkixNFMxOjV:L3G+

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pSMAD1 / pSMAD5 / pSMAD8 / SMAD1 / SMAD5 / SMAD8 / ID1 / SMAD4 / PARP / Cleaved PARP; 

PubMed: 31098401     


In vitro molecular pharmacology of LDN-193189 and LDN-214117. Western blot analysis of time- and concentration-dependent effects on downstream signalling in response to a LDN-193189 and b LDN-214117 in DIPG cells. Increasing concentrations (0–10 µM) at 4 and 8 h are shown for SU-DIPG-VI, HSJD-DIPG-IV and HSJD-DIPG-007. GAPDH is the loading control.

31098401
Immunofluorescence
Tbx18 / Hcn4; 

PubMed: 30906456     


Representative immunofluorescence microscopy images of epicardial progenitor cells from the four groups with staining for Hcn4 (red). The nuclei were counterstained with DAPI (blue) and the YFP expressed by the cells is apparent (scale bar, 50 µm). (Tbx18 was conjugated to YFP).

30906456
Growth inhibition assay
Cell viability; 

PubMed: 31098401     


Screening of ALK2 inhibitors in vitro. Concentration-response curves for eight ALK2 inhibitors tested against three ACVR1 mutant cell cultures (HSJD-DIPG-007 (R206H), SU-DIPG-IV (G328V), HSJD-DIPG-018 (R258G), purple) and two wild-type cultures (SU-DIPG-VI, QCTB-R059, grey). a Pyrazolo[1,5-a]pyrimidines—dorsomorphin, LDN-193189, DMH1, LDN-212854. b Pyridines—K02288, LDN-214117, LDN-213844, LDN-213819. Concentration of compound is plotted on a log scale (x-axis) against cell viability (y-axis). Mean plus standard deviation are plotted from at least n = 3 experiments.

31098401
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]

Protocol

Animal Research:

[1]

- Collapse
  • 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.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO Insoluble
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 406.48
Formula

C25H22N6

CAS No. 1062368-24-4
Storage powder
in solvent
Synonyms DM3189
Smiles C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC6=CC=CC=C56)N=C3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID