Uses
4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline Hydrochoride is a selective inhibitor of bone morphogenetic protein (BMP) pathway, useful in the treatment of diseases.
Uses
LDN-193189 HCl has been used to inhibit BMP type I receptor activity to study the pathogenesis of fibrodysplasia ossificans progressive, a congenital hyperossification disorder, and to examine the role of osteogenesis in prostate tumor metastases in bone.
Biological Activity
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].
References
[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.
