LDN-193189

Catalog No.S2618

LDN-193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β.

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LDN-193189 Chemical Structure

LDN-193189 Chemical Structure
Molecular Weight: 406.48

Validation & Quality Control

Customer Product Validation(3)

Quality Control & MSDS

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Product Description

Biological Activity

Description LDN-193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β.
Targets ALK2 [1]
(C2C12 cells)
ALK3 [1]
(C2C12 cells)
IC50 5 nM 30 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
C2C12MkLpT4lv[XOnIFHzd4F6Mn\RbY5pcWKrdIOgeIhmKGurbnHz[UBi[3Srdnn0fUBw\iCDTFu0JIFv\CCDY4TSTWlCKHerdHigTWM2OMLidnHseYV{KG:oIEGwNUBidmRiMkGwJI5uNCC{ZYPw[YN1cX[nbIm=M2Hj[lI2OzZ6M{Ky
EOC216MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHvGZ|UxNjFvMUCg{txONWjiToNOOi1zMDDkM3;V[2ROW09?M2S4d4lv\HWlZTDj[YxtKGSnYYToJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXyMVKyOVIzPzh7Mx?=
OVAC429M4LmWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEjsfmYzNzVizszNM{K4PFQ5KGh?NXSwbGV4TE2VTx?=M3\3NYRm[3KnYYPld{B1cGVicHXyZ4VvfGGpZTDv[kBk\WyuczDpckBUKHCqYYO=M{Dw[lI2OjJ5OEmz
SKOV3M360U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkfYNk82KM7:TR?=MkToOFghcA>?MlnBSG1UVw>?MVjk[YNz\WG|ZYOgeIhmKHCncnPlcpRi\2Vib3[gZ4VtdHNiaX6gV{BxcGG|NIDDWWUzPTJ{N{i5Ny=>
OVCA429MnTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUGyM|Uh|ryPNFvKXHE1QCCqMl6zSG1UVw>?M4rtOYRm[3KnYYPld{B1cGVicHXyZ4VvfGGpZTDv[kBk\WyuczDpckBUKHCqYYO=M1;YWlI2OjJ5OEmz
EOC219NFTCSYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHTCN|czNzVizszNNWP3cnBYPDhiaB?=MlHPSG1UVw>?NUfpbXd6\GWlcnXhd4V{KHSqZTDw[ZJk\W62YXflJI9nKGOnbHzzJIlvKFNicHjhdy=>MonHNlUzOjd6OUO=
A549Mk\OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NETWSnExNjVvMU[g{txOMnL2SG1UVw>?MV3pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>MmnTNlQ4PzhyMUG=
BEAS-2B MoH5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWqwMlUuOTZizszNNXflVnZZTE2VTx?=MV;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>MnjvNlQ4PzhyMUG=
hBMSCsMYnGeY5kfGmxbjDBd5NigQ>?MmrXNE4zyqEQvF2=NH3qSYc4KGR?NWXTVYd{[WKxbHnzbIV{KHSqZTDzbYxq[mmwaX6tdJJwdW:2ZXSgRWxRKGGldHn2bZR6yqCyYYL0cJk>Mny4NlQxPzZzOEe=
PANC-1M2rqUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlnuOU02ODBibl2=NUCzVm1zPDhiaB?=NGTZOWlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?NHT2V2UzOzl4OUeyPS=>
MIA PaCa-2M1rHN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2DJSlUuPTByIH7NMWm0PEBpMYDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>NFXTWVgzOzl4OUeyPS=>
Bx-PC3MknnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1fWTFUuPTByIH7NMX20PEBpMkLFbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>MmXZNlM6Pjl5Mkm=
PC3 MYjGeY5kfGmxbjDBd5NigQ>?M4HaUlUxOCCwTR?=NHvkWJEzKGh?MWXy[ZBz\XO|ZYOgZYN1cX[jdHnvckBw\iCVbXHkNU82NzhiYX7kJHAuW22jZEOgcIV3\Wy|MWSyNlQ2Ojh6Mx?=
LNCaPNFn6OmFHfW6ldHnvckBCe3OjeR?=NWHKeIVkOOLCk{WwNEBvVQ>?NYrJTnhxOiCqM2\3fJJmfmW{c3XzJJJieGGveXPpck1qdmS3Y3XkJINmdGxiZHXheIg>NH75e2UzOjR3Mki4Ny=>
EOCNGPoZ5NHfW6ldHnvckBCe3OjeR?=NVvKUJpOOTBvMUCwNEBvVQ>?MUe3NkBpMlPXdoVlfWOnczD0bIUheGixc4Doc5J6dGG2ZXSgRm1RKFJvU33h[FEwPS96wrC=NF\6O5ozOjJ2OUSxOS=>
HaCaT NUS2cW1xTnWwY4Tpc44hSXO|YYm=M1;qOlAvODBzLUGwJO69VQ>?M1HT[VIhcA>?M{XXfYlvcGmkaYTzJGJOWDJvaX7keYNm\CCyaH;zdIhwenmuYYTpc44hd2ZiU33h[FEwPS96IIfpeIgh[W5iSVO1NOKhd2ZifkCuNFA2yqEQvF2=MXiyNVc1ODl4Nh?=
HaCaT MWLGeY5kfGmxbjDBd5NigQ>?MnjsNE4xODFvMUCg{txOMnK0NkBpMX\pcohq[mm2czD0bIUh[WKrbHn0fUBw\iCDTFuyJJRwKHCqb4PwbI9zgWyjdHWgS3NVNVOvYXSxxsB4cXSqIHHuJGlEPTEEoH;mJFQ2yqCwTR?=MUOyNVc1ODl4Nh?=
HaCaT Ml\CSpVv[3Srb36gRZN{[Xl?MlWyNE4xODFvMUCg{txOMV2yJIg>M1P1SolvcGmkaYTzJJRp\SCjYnnsbZR6KG:oIFHMT|MhfG9icHjvd5Bpd3K7bHH0[UBUdWGmMdMge4l1cCCjbjDJR|UxyqCxZjCxNFAhdk1?MUiyNVc1ODl4Nh?=
HaCaT NFLRTXNHfW6ldHnvckBCe3OjeR?=MnTBNE4xODFvMUCg{txONFy1ZnczKGh?MX3pcohq[mm2czDBUGs1KGGwZDDBUGs2KHerdHigTWM2OMLidnHseYV{KG:oIECuN:Kh|ryPIHHu[EAxNjYEoN88UUBz\XOyZXP0bZZmdHl?NGSwZ|czOTd2MEm2Oi=>

... Click to View More Cell Line Experimental Data

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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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.

Animal Study: [1]

Animal Models Ad.Cre on P7 is injected into conditional caALK2–transgenic and wild-type mice.
Formulation LDN193189 is dissolved in DMSO and then diluted in water.
Dosages ≤3 mg/kg
Administration Administered via i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[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.

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Chemical Information

Download LDN-193189 SDF
Molecular Weight (MW) 406.48
Formula

C25H22N6

CAS No. 1062368-24-4
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms DM3189
Solubility (25°C) * In vitro DMSO <1 mg/mL (<1 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo Saline (suspension) 30mg/mL
* <1 mg/ml means slightly soluble or 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 Name 4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

Customer Product Validation (3)


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Rating
Source J Cell Sci, 2013, 126: 234-43. LDN-193189 purchased from Selleck
Method Western Blot
Cell Lines Primary rib chondrocytes
Concentrations 100/200 nM
Incubation Time 24 h
Results LDN-193189 can partially reverse the increased phospho-Smad1/5 expression in Jab1flox/flox, Col2a1-Cre mutant chondrocytes in a dose-dependent manner.

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Rating
Source Int J Cancer 2014 136(5):E455-69. LDN-193189 purchased from Selleck
Method Immunocytochemistry
Cell Lines OVCA429 cells
Concentrations 2, 5 uM
Incubation Time 6 h
Results Initiation of cell death at an early time point (6 hr) was confirmed by treating OVCA429 cells with the cell permeable viability dye AO and EB that is only able to pass membranes of dead or dying cells. A statistically significant difference in the percent of cells staining positively was observed with 10 mM LDN.

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Rating
Source Dev Biol 2014 378:107-121. LDN-193189 purchased from Selleck
Method Immunocytochemistry and in situ hybridization
Cell Lines Zebrafish
Concentrations 2 uM
Incubation Time 24 h
Results The distribution and number of Pax7-expressing cells at 24 h was different between controls and sulf1 morphants, which we quantified at the 15th somite at 24 hpf. When treated with LDN, there was obviously decreasd expressing of Pax7,comparing with controls.

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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