Description
LDN-212854 is a potent and selective BMP receptor inhibitor with IC50 of 1.3 nM for ALK2, about 2-, 66-, 1641-, and 7135-fold selectivity over ALK1, ALK3, ALK4, and ALK5, respectively.
In vitro
In myofibroblast C2C12 cells, LDN-212854 exhibits greater selectivity for BMP6-versus BMP4-induced osteogenic differentiation.
In vivo
LDN-212854 (6 mg/kg, i.p.) effectively neutralize ALK2 signaling in vivo, and potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva.
Uses
5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline, contains the pyrazolo[1,5-a]pyrimidine scaffold, acting as a novel and selective bone morphogenetic protein receptor (BMP) inhibitors. It is a COVID19-related research product.
Biological Activity
ldn-212854 is a selective inhibitor of bone morphogenetic protein (bmp) signaling with ic50 value of 1.2nm [1].in the kinase assay, ldn-212854 shows inhibitory activities against caalk2 and caalk5 with ic50 values of 16nm and 2μm, respectively. it demonstrates that ldn-212854 is selective against bmp over tgf-β signaling. besides that, the inhibition of caalk2 caused by ldn-212854 is 6- and 10-fold more potent than that of caalk1 and caalk3, respectively. in c2c12 cells transfected with bmp receptors, ldn-212854 also exerts preferential inhibition against caalk2. furthermore, in a transgenic alk2q207d model of heterotopic ossification, treatment of ldn-212854 prevents the formation of heterotopic bone and preserves limb range of motion [1].
Biochem/physiol Actions
LDN-212854 is also known as 5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline. LDN-212854 prevents heterotopic ossification in an inducible mutant ALK2 (activin receptor-like kinase 2).
References
[1] mohedas a h, xing x, armstrong k a, et al. development of an alk2-biased bmp type i receptor kinase inhibitor. acs chemical biology, 2013, 8(6): 1291-1302.
