LDN-193189 2HCl (DM-3189 2HCl) is a selective BMP signaling inhibitor that inhibits ALK1,ALK2,ALK3 and ALK6, showing IC50s of 0.8 nM, 0.8 nM, 5.3 nM, and 16.7 nM, respectively, in kinase assays.LDN-193189 2HCl inhibited the transcriptional activity of BMP type I receptors in C2C12 cells, with IC50s of 5 nM and 30 nM, respectively. LDN-193189 2HCl inhibited the transcriptional activity of BMP type I receptors ALK2 and ALK3 in C2C12 cells, with IC50s of 5 nM and 30 nM, respectively, and was 200-fold more selective for BMP than for TGF-β.

LDN193189 can effectively inhibit BMP4-mediated activation of Smad1, Smad5, and Smad8, with IC50 of 5 nM. It can also effectively inhibit the transcriptional activity of BMP type I receptors ALK2 and ALK3, with IC50 of 5 nM and 30 nM, respectively. LDN193189 also has an inhibitory effect on transcriptional activation induced by persistently activated ALK2R206H or ALK2Q207D mutant proteins.[1]
A recent study showed that LDN-193189 blocks the production of oxidative free radicals induced by oxidized LDL in human arterial endothelial cells.[4]

LDN-193189 (3 mg/kg, intraperitoneal injection; birth in conditional caALK2) caused weak calcification of the left tibia and fibula, which was visible on day 13 and blocked on day 15 without causing weight loss or growth retardation, spontaneous fractures, decreased bone density, or abnormal behavior.[1]
LDN193189 forms curved Zebrafish embryos by inhibiting the signal pathway induced by bone morphogenetic protein (BMP) 6 and has no effect on vascular development.[2]
In mice with PCa-118b tumors, LDN-193189 treatment slowed down tumor growth and reduced bone formation in the tumor.[3]
In LDLR -/- mice, LDN-193189 inhibited the development of arterial atherosclerosis. In addition, LDN-193189 has inhibitory effects on vascular inflammation, osteogenic activity, and calcification.[4]