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LDN193189

SKU: orb1227048

Description

LDN193189 is a potent, selective BMP type I receptor that inhibits BMP4-induced phosphorylation of SMAD1/5/8 with IC50 of 5 nM, displays >200-fold selectivity for BMP signaling over TGF-β signaling (IC50>1,000 nM); efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 (IC50=5 nM and 30 nM, respectively), with weaker effects on activin and the TGF-β type I receptors ALK4, ALK5 and ALK7; also blocks the transcriptional activity induced by either constitutively active ALK2 R206H or ALK2 Q207D mutant proteins, affects BMP-induced osteoblast differentiation, attenuates ectopic ossification in vivo.(In Vitro):LDN193189 (GMP) (250 nM; 0-7 d) induces human pluripotent stem cells (hPSC) directly differentiates into midbrain dopamine neurons (mDA).LDN193189 (GMP) (200 nM) induces the generation of glucose-responsive β cells from hPSCs in vitro.

Images & Validation

Key Properties

CAS Number1062368-24-4
MW406.4824
Purity>98% (HPLC)
FormulaC25H22N6
SMILESC1CN(CCN1)C1=CC=C(C=C1)C1=CN2N=CC(=C2N=C1)C1=CC=NC2=CC=CC=C12
TargetALK
SolubilityEthanol: 0.25 mg/mL (Need ultrasonic and warming); DMSO: < 0.1 mg/mL; H2O: < 0.1 mg/mL

Bioactivity

In Vivo
LDN-193189 (i.p.; 3 mg/kg; daily; for 35 days) might affect the interaction between breast cancer cells and the bone environment. LDN-193189 (i.p.; 3 mg/kg; single) shows a reduction in ectopic ossification and functional impairment. Animal model: Ahymic NMRI nude female mice (6-week-old). Dosage: 3 mg/kg. Administration: Itraperitoneal, daily, for 35 days. Result: Ehanced etastases development In vivo. Animal model: C57BL/6 mice. Dosage: 3 mg/kg. Administration: Intraperitoneal, single. Result: Diminished ectopic bone formation and preserved joint spaces over the same interval without inducing fractures, osteopenia or skeletal abnormalities.
In Vitro
LDN-193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 values of 5 nM and 30 nM, respectively. LDN-193189 has weake effects on activin and the TGF-β type I receptors ALK4, ALK5 and ALK7 with IC50 values of ≥ 500 nM. LDN-193189 binds ActRIIA with Kd value of 14 nM. LDN-193189 (0.5 μM; 30 min) targets GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. LDN-193189 (0.05, 0.5, 5 μM) efficiently inhibits GDF8 induced Smad3/4 reporter gene activity. LDN-193189 (0-5 μM) rescues myogenesis in myoblasts treated with GDF8. Western blot analysis. Cell line: Primary human myoblasts, C2C12 cells. Concentration: 0.5 μM Incubation time: 30 min. Result: Inhibited GDF8-induced signaling pathways in undifferentiated and in differentiated primary human myoblasts and in C2C12 premyoblasts.

Storage & Handling

StorageStorage temperature: -20°C. Stability: ≥ 2 years
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

LDN 193189 | LDN-193189 | DM-3189

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Quality Guarantee

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LDN193189 (orb1227048)

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500 mg
2 mg
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25 mg
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100 mg
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200 mg
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