product name LDN-193189 HCl
Description: LDN193189 HCl is the hydrochloride salt of LDN193189, which is a selective and highly potent small molecule BMP signaling inhibitor, and inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM in C2C12 cell lines, respectively, it shows 200-fold selectivity for BMP versus TGF-β. 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.
References: Nat Med. 2008 Dec;14(12):1363-9; Br J Pharmacol. 2010 Sep;161(1):140-9.
442.94
Formula
C25H22N6.HCl
CAS No.
1062368-62-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 52 mg/mL (117.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| 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: Cell Assay: |
|---|---|
| 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. 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 model | Ad.Cre on P7 is injected into conditional caALK2–transgenic and wild-type mice |
| Formulation & Dosage | Dissolved 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 |
