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LDN193189 is a cell-permeable, highly potent and selective BMP pathway inhibitor by inhibiting BMP type I receptors ALK2 (IC₅₀=5 nM) and ALK3 (IC₅₀=30 nM), but not ALK4, ALK5, and ALK7 (> 0.5 µM). It prevents Smad1, Smad5, and Smad8 phosphorylation. It is a useful tool compound to modulate stem cell differentiation (for example, neural differentiation of human ESC/iPSC in combination with SB431542). It was also used in animal models to treat FOP and ectopic ossification, as well as NSCLC lung cancer.

How to Use:

• In vitro: LDN-193189 is typically used at 0.1 µM final concentration in stem cell differentiation conditions.
• In vivo: Intraperitoneal (IP) administration of 3 mg/kg LDN-193189 was used once or twice daily.

Reference: 

• 1.  Cuny GD, et al.  Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors. (2008), Bioorg Med Chem Lett. 18(15):4388-92.
• 2.  Paul B Yu, et al. BMP type I receptor inhibition reduces heterotopic ossification. (2008), Nature Med. 14: 1363-1369.
• 3.  Yu PB, et al.  Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. (2008), Nature Chem Biol. 4: 33-41.
• 4.  Chambers SM, et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. (2009), Nature Biotechnology 27, 275-280.
• 5.  Boergermann JH, et al. Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells. (2010), Int J Biochem Cell Biol. 42(11):1802-7.
• 6.  Lee YC, et al. BMP4 promotes prostate tumor growth in bone through osteogenesis.  (2011), Cancer Res 71:5194-5203.
• 7.  Najm FJ, et al. Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells. (2011) Nature Methods 8, 957–962

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