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LDN-193189 4HCl
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
LDN-193189 4HCl图片
CAS NO:1062368-62-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)552.33
FormulaC25H26Cl4N6
CAS No.1062368-62-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 1~20 mg/mL, vary from batch to batch
Water: 50-100 mg/mL
Ethanol: <1 mg/mL
SMILES CodeC1(C2=C3N=CC(C4=CC=C(N5CCNCC5)C=C4)=CN3N=C2)=CC=NC6=CC=CC=C16.Cl.Cl.Cl.Cl
SynonymsDM3189 4HCl; LDN193189 4HCl; DM-3189 4HCl; LDN 193189 4HCl; DM 3189 4HCl; LDN-193189 4HCl
实验参考方法
In Vitro

In vitro activity: 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. 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.


Kinase Assay: LDN193189 is a selective BMP type I receptor inhibitor, which efficiently inhibits ALK2 and ALK3 (IC50=5 nM and 30 nM, respectively), with weaker effects on ALK4, ALK5 and ALK7 (IC50≥500 nM).


Cell Assay: Mouse PASMCs grown are transiently transfected to 50% confluence in six-well plates with 0.3 μg Id1promoter luciferase reporter construct (BRE-Luc) in combination with 0.6 μg of plasmid expressing constitutively active forms of BMP type I receptors (caALK2, caALK3 or caALK6). For both reporter plasmids, 0.2 μg of pRL-TKRenilla luciferase are used to control for transfection efficiency. PASMCs are incubated with LDN193189 (2 nM-32 μM) or vehicle starting 1 h after transfection. Cell extracts are harvested and quantified relative promoter activity by the ratio of firefly to Renilla luciferase activity with the dual luciferase assay kit.

In VivoIn 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. LDN193189 dorsalizes zebrafish embryos by inhibiting signaling pathways induced by bone morphogenetic protein (BMP)6 without effect on vascular development. In PCa-118b tumor-bearing mice, LDN-193189 treatment attenuates tumor growth and reduces bone formation in the tumors. 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.
Animal modelAd.Cre on P7 is injected into conditional caALK2–transgenic and wild-type mice
Formulation & DosageDissolved in DMSO and then diluted in water; 3 mg/kg; i.p. injection
References

Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52