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].
参考文献:
[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.
Protocol
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Cell experiment [1]:
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Cell lines
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C2C12 cells
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Preparation method
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The solubility of this compound in DMSO is >2.1mg/mL. 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.
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Reacting condition
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100 nM, 0-72h
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Applications
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LDN-193189 inhibited the induction of alkaline phosphatase activity in C2C12 cells by BMP4 even when administered 12 h after BMP stimulation.
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Animal experiment [2, 3]:
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Animal models
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Conditional caALK2-transgenic mice, PCa-118b tumor-bearing mice
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Dosage form
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Intraperitoneal administration, 3 mg/kg
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Application
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In conditional caALK2-transgenic mice with Ad.Cre on on postnatal day 7 (P7), LDN-193189 (3 mg/kg, i.p.) led to mild calcifications surrounding the left tibia and fibula first visible at P13, and prevented radiographic lesions at P15 without causing weight loss or growth retardation, spontaneous fractures, decreased bone density or behavioral abnormalities. In PCa-118b tumor-bearing mice, LDN-193189 treatment attenuated tumor growth and reduced bone formation in the tumors.
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Other notes
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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.
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参考文献:
[1]. 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.
[2]. Paul B Y, Deng D Y, Lai C S, et al. BMP type I receptor inhibition reduces heterotopic ossification[J]. Nature medicine, 2008, 14(12): 1363-1369.
[3]. Lee Y C, Cheng C J, Bilen M A, et al. BMP4 promotes prostate tumor growth in bone through osteogenesis[J]. Cancer research, 2011, 71(15): 5194-5203.
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