LDN-193189 is a highly potent small molecule inhibitor of bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 with IC50 values of 5 nM and 30 nM, respectively. BMPs induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. BMP signaling pathway is the key regulators of cell fate decisions during embryogenesis and tissue homeostasis. LDN-193189 inhibits ectopic ossification and a potential agent in the treatment of NSCLC lung tumors, showing significant in vivo clinical utility. In addition, it inhibits the activation of p38, ERK1/2 and Akt in C2C12 cells. LDN-193189 only weakly inhibits ALK4, ALK5, and ALK7. LDN-193189 affects not only the Smad but also the non-Smad signalling pathways induced by either BMP2, BMP6 or GDF5.
Theriogenology. 2024 Mar 15;219:65-74.
Growth differentiation factor 9 regulates the expression of estrogen receptors via Smad2/3 signaling in goat cumulus cells
LDN-193189 purchased from AbMole
Ann Transl Med. 2021 Jul;9(13):1087.
Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation
LDN-193189 purchased from AbMole
 |
Source | J Biol Chem (2015). Figure 4. LDN-193189 |
| Method | immunoblotting | |
| Cell Lines | C2C12 cells | |
| Concentrations | 5 μM | |
| Incubation Time | 30 min | |
| Results | Pretreatment with dorsomorphin or LDN-193189 led to reduced levels of phosphorylated Smad2/3 following GDF8 stimulation (Fig. 4A), which were comparable with their effects on BMP2-induced phosphorylation of Smad1/5 (Fig. 4B), whereas there was no effect on TGF- induced Smad2/3 signals (Fig. 4A). |
 |
Source | J Biol Chem (2015). Figure 2. LDN-193189 |
| Method | immunoblotting | |
| Cell Lines | C2C12 cells | |
| Concentrations | 0.5 μM | |
| Incubation Time | 30 min | |
| Results | A similar effect of dorsomorphin and LDN-193189 treatment was observed in undifferentiated primary human myoblasts as well as in the mouse myoblast cell line C2C12 |
| Cell Experiment | |
|---|---|
| Cell lines | C2C12 cells |
| Preparation method | Alkaline phosphatase activity 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 (Sigma) 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, Promega), using replicate wells treated identically to those used for alkaline phosphatase measurements. |
| Concentrations | 0,2,8,31,125,500nM |
| Incubation time | 6 days |
| Animal Experiment | |
|---|---|
| Animal models | C57BL/6 mouse FOP model |
| Formulation | unknown |
| Dosages | 3 mg /kg every 12 h |
| Administration | intraperitoneally |
| Molecular Weight | 406.48 |
| Formula | C25H22N6 |
| CAS Number | 1062368-24-4 |
| Solubility (25°C) | Water ≥4 mg/mL (Need warming) |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
| Related ALK Products |
|---|
| NVL-655
NVL-655 is a novel, brain-permeable, selective ALK inhibitor with antitumor activity. For Ba/F3 CLIP1-LTK cells, NVL-655 has an IC50 of 2.7 nM. It can be used in studies related to ALK-positive non-small cell lung cancer (NSCLC). |
| APG-2449
APG-2449 is an orally active, potent ALK/ROS1/FAK inhibitor with anti-tumor activity in a mouse model of non-small cell lung cancer (NSCLC). |
| ALK2-IN-5
ALK2-IN-5, pyrazolopyrimidine compound, is an ALK2 inhibitor. |
| J-1048
J-1048 is an activin receptor-like kinase 5 (ALK5) inhibitor. |
| CPD-1224
CPD-1224 is an orally active derivative of ALK inhibitors to cereblon ligands. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
