A8324-10mg | LDN-193189 [1062368-24-4] Clinisciences

Background

LDN193189 is a selective transcriptional activity morphogenetic protein (BMP) type I receptors inhibitor. It inhibits activin receptor-like kinase-2 (ALK2) and ALK3 with IC50 values of 5 nM and 30 nM, respectively [1].

LDN193189 has been showed to inhibit BMP induced phosphorylation of Smad signaling (Smad1/5/8) and non-Smad signaling including p38 and Akt in C2C12 cells [2].

Pharmacological inhibition of BMP by LDN193189 has shown to prevent down-regulation of E-cadherin in response to BMP2 both in bronchial epithelial (Beas2B) cells and in C57BL/6 mice. LDN193189 also inhibits the BMP-induced reduction of epithelial permeability at cellular level [3].

References:
[1] Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9.
[2] Boergermann JH1, Kopf J, Yu PB, Knaus P. Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells. Int J Biochem Cell Biol. 2010 Nov;42(11):1802-7.
[3] Helbing T1, Herold EM, Hornstein A, Wintrich S, Heinke J, Grundmann S, Patterson C, Bode C, Moser M. Inhibition of BMP activity protects epithelial barrier function in lung injury. J Pathol. 2013 Sep;231(1):105-16. doi: 10.1002/path.4215. Epub 2013 Jul 10.

Product Citation

1. Michael Raymond, Warren Vieira, et al. "Development of a model system to study the regulation of patterning competency in regenerating axolotl limbs." Research Square. 07 Dec, 2023.
2. Wai Kit Chan, Danilo Negro, et al. "Loss of PAX6 alters the excitatory/inhibitory neuronal ratio in human cerebral organoids." bioRvix. August 01, 2023.
3. Xiaoya An, Guoliang Wang, et al. "Novel cell culture paradigm prolongs mouse corneal epithelial cell proliferative activity in vitro and in vivo." Front Cell Dev Biol. 2021 Jun 30;9:675998. PMID: 34277619
4. Xin Yu, Shiguang Li, et al. "Androgen Maintains Intestinal Homeostasis by Inhibiting BMP Signaling via Intestinal Stromal Cells." Stem Cell Reports. 2020 Oct 13;15(4):912-925. PMID: 32916121
5. Xiaohong Zhang, Xueshuang Xing, et al. "Ionizing radiation induces ferroptosis in granulocyte-macrophage hematopoietic progenitor cells of murine bone marrow." Int J Radiat Biol , 1-35 2020 Jan 6. PMID: 31906761

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	406.48
Cas No.	1062368-24-4
Formula	C₂₅H₂₂N₆
Synonyms	LDN 193189;LDN193189
Solubility	insoluble in DMSO; insoluble in EtOH; insoluble in H2O
Chemical Name	4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline
SDF	Download SDF
Canonical SMILES	C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC6=CC=CC=C56)N=C3
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	C2C12 myofibroblast cells; bronchial epithelial (Beas2B) cells
Preparation method	This compound is limited soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	0.005-5 μM. 30-60 min
Applications	LDN-193189 inhibited both BMP induced Smad1/5/8 phosphorylation and BMP-mediated induction of the p38 MAPK, Erk1/2 and Akt pathway in C2C12 cells. LDN-193189 dose-dependently inhibited the activation of Smad1/5/8, p38 and Akt. LDN-193189 induced a strong increase in phosphorylated p38 MAPK levels and a slight increase in p-Akt in C2C12 cells. LDN (10 μM, 60 min) induced p38 and Akt phosphorylation. LDN (0.5 μM, 30 min) inhibited BMP-mediated Smad1/5/8, p38, ATF2 and CREB phosphorylation.
Animal experiment [2]:
Animal models	C57BL/6 mice
Dosage form	Intraperitoneal injection; 3 mg/kg every 12 h
Application	In Ad.Cre-injected, caALK2-expressing mice, treatment with LDN-193189 prevented radiographic lesions at P15. LDN-193189–treated mice appeared to preserve knee and ankle joints at P30 and P60. LDN-193189-treated mice showed no ectopic bone at P15 but did show enhanced cartilage formation in surrounding soft tissues. LDN-193189–treated mice showed mildly impaired range of motion even in the absence of radiographically visible disease at P30.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9. [2]. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9.

Biological Activity

Description	LDN193189 is a selective inhibitor of BMP signaling for the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively.
Targets	ALK2	ALK3
IC50	5 nM	30 nM