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Purity: ≥98%
LDN-193189 (also called LDN193189; DM-3189; DM3189) is a highly potent and selective small molecule inhibitor of the BMP (bone morphogenetic protein) signaling pathway with potential antineoplastic activity. It inhibits the transcriptional activity of the BMP type I receptor kinases such as ALK2 (activin receptor-like kinase-2) and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively. LDN-193189 exhibits 200-fold selectivity for BMP over TGF-β. LDN-193189 also exhibits the inhibitory effects on associated vascular inflammation, osteogenic activity, and calcification.
| Targets |
ACVR1 (IC50 = 5 nM); BMPR1A (IC50 = 30 nM); ALK2 (IC50 = 5 nM), ALK3 (IC50 = 30 nM)[1]
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| ln Vitro |
Human pluripotent stem cells (hPSCs) are stimulated by LDN193189 (GMP) (250 nM; 0-7 d) to develop directly into midbrain dopamine neurons (mDA)[1]. In vitro, hPSCs are induced to produce glucose-responsive β cells by LDN193189 (GMP) at a concentration of 200 nM[2].
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| ln Vivo |
LDN-193189 (ip; 3 mg/kg; daily; 35 days) may have an impact on how breast cancer cells interact with their surroundings in the bone[3]. LDN-193189 (ip; 3 mg/kg; single) reduces functional impairment and ectopic ossification [1].
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| Enzyme Assay |
Alkaline phosphatase activity[1]
We seeded C2C12 cells into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. We treated the wells in quadruplicate with BMP ligands and LDN-193189 or vehicle. We collected the cells after 6 d in culture in 50 μl Tris-buffered saline and 1% Triton X-100. We added the lysates to p-nitro-phenylphosphate reagent in 96-well plates for 1 h and then evaluated alkaline phosphatase activity (absorbance at 405 nm). We measured cell viability and quantity by Cell Titer Aqueous One (absorbance at 490 nm), using replicate wells treated identically to those used for alkaline phosphatase measurements.
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| Cell Assay |
Cell culture [1]
We isolated PASMCs from wild-type and CAG-Z-EGFP-caALK2–transgenic mice as previously described and cultured them in RPMI medium supplemented with 10% FBS. We induced recombination of PASMCs expressing conditional caALK2 in vitro by infecting with Ad.Cre (multiplicity of infection of 50) or Ad.GFP as a control and then culturing for 3 d and passaging. We cultured C2C12 myofibroblast cells (American Type Culture Collection) in DMEM supplemented with glutamine and 10% FBS. We preincubated cells with pharmacological inhibitors for 10 min and then exposed them to BMP4, TGF-β or platelet-derived growth factor-BB ligands for 30 minutes at 37 °C.[1]
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| Animal Protocol |
Animal/Disease Models: Ahymic NMRI nude female mice (6weeks old)[3]
Doses: 3 mg/kg Route of Administration: Itraperitoneal, daily, for 35 days Experimental Results: Ehanced etastases development in vivo. Animal/Disease Models: C57BL/6 mice[1] Doses: 3 mg/kg Route of Administration: Intraperitoneal, single Experimental Results: Diminished ectopic bone formation and preserved joint spaces over the same interval without inducing fractures, osteopenia or skeletal abnormalities. |
| References |
[1]. Nat Med.2008 Dec;14(12):1363-9.
[2]. Br J Pharmacol.2010 Sep;161(1):140-9. [3]. Cancer Res, 2011, 71(15), 5194-5203. [4]. Int J Clin Exp Pathol. 2014 Jul 15;7(8):4674-84. |
| Additional Infomation |
4-[6-[4-(1-piperazinyl)phenyl]-3-pyrazolo[1,5-a]pyrimidinyl]quinoline is a member of pyrimidines.
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| Molecular Formula |
C25H22N6
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|---|---|
| Molecular Weight |
406.48
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| Exact Mass |
406.19
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| Elemental Analysis |
C, 73.87; H, 5.46; N, 20.67
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| CAS # |
1062368-24-4
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| Related CAS # |
LDN193189;1062368-24-4
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| PubChem CID |
25195294
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| Appearance |
Typically exists as light yellow to yellow solids at room temperature
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.740
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| LogP |
1.81
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
587
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C2C([H])=C([H])C(C3C([H])=NC4=C(C([H])=NN4C=3[H])C3=C([H])C([H])=NC4=C([H])C([H])=C([H])C([H])=C34)=C([H])C=2[H])C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H]
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| InChi Key |
CDOVNWNANFFLFJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22N6/c1-2-4-24-22(3-1)21(9-10-27-24)23-16-29-31-17-19(15-28-25(23)31)18-5-7-20(8-6-18)30-13-11-26-12-14-30/h1-10,15-17,26H,11-14H2
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| Chemical Name |
4-[6-(4-Piperazin-1-yl-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline
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| Synonyms |
DM3189; LDN193189; DM-3189; 4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline; 4-[6-(4-Piperazin-1-Ylphenyl)pyrazolo[1,5-A]pyrimidin-3-Yl]quinoline; LDN 193189; W69H5YQU9O; CHEMBL513147; LDN 193189; DM 3189; LDN-193189
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.2 mg/mL (2.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.2 mg/mL (2.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: Saline (suspension): 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4601 mL | 12.3007 mL | 24.6015 mL | |
| 5 mM | 0.4920 mL | 2.4601 mL | 4.9203 mL | |
| 10 mM | 0.2460 mL | 1.2301 mL | 2.4601 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Inhibitor binding to ActRII.J Biol Chem.2015 Feb 6;290(6):3390-404.
Dorsomorphin and LDN-193189 inhibit GDF8-induced signaling pathways in undifferentiated and in differentiated primary human myoblasts and in C2C12 premyoblasts.J Biol Chem.2015 Feb 6;290(6):3390-404. |
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Ligand-specific effects of kinase inhibitors on Smad2/3 and Smad1/5 phosphorylation.
Dorsomorphin treatment facilitates myotube formation.J Biol Chem.2015 Feb 6;290(6):3390-404. |
Dorsomorphin and LDN-193189 efficiently inhibit GDF8 induced Smad3/4 reporter gene activity.J Biol Chem.2015 Feb 6;290(6):3390-404. |
Dorsomorphin and LDN-193189 counteract GDF8-induced repression of myogenic differentiation.J Biol Chem.2015 Feb 6;290(6):3390-404. |
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Dorsomorphin and LDN-193189 promote the formation of a contractile myotube network.J Biol Chem.2015 Feb 6;290(6):3390-404. |
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