LDN193189 Tetrahydrochloride 是一种选择性的BMPI 型受体抑制剂，抑制ALK2和ALK3的IC50分别为 5 nM 和 30 nM。对 ALK4，ALK5 和 ALK7 的作用效果弱 (IC50≥500 nM)。

LDN193189 Tetrahydrochloride is a selective BMP type I receptor inhibitor, which efficiently inhibits ALK2 and ALK3 ( IC 50 =5 nM and 30 nM, respectively), with weaker effects on ALK4, ALK5 and ALK7 (IC 50 ≥500 nM) [1].

LDN193189 inhibits BMP4-mediated Smad1, Smad5 and Smad8 activation with greater potency than did dorsomorphin (IC 50 =5 nM versus 470 nM) while retaining 200-fold selectivity for BMP signaling versus TGF-β signaling (IC 50 for TGF-β ≥1,000 nM). LDN193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 (IC 50 =5 nM and 30 nM, respectively), and the TGF-β type I receptors ALK4, ALK5 and ALK7 (IC 50 ≥500 nM) and increases selectivity for BMP signaling versus AMP-activated protein kinase, PDGFR and MAPK signaling pathways as compared to the parent compound. LDN193189 blocks the transcriptional activity induced by either constitutively active ALK2 R206H or ALK2 Q207D mutant proteins. These findings suggest that LDN193189 might affect BMP-induced osteoblast differentiation. In fact, LDN193189 inhibits the induction of alkaline phosphatase activity in C2C12 cells by BMP4 even when administered 12 h after BMP stimulation, indicating sustained BMP signaling activity is needed for osteogenic differentiation [1].

In the first experiment, LDN193189 (3 mg/kg) is injected intraperitoneally twice a day after tumors became palpable 7 days post-implantation. The growth rates between the control vehicle- and LDN193189-treated mice are not significantly different after the first 5 weeks, but differences in the growth rates are detected after 6 and 7 weeks post-treatment. In the second experiment, cells are isolated from PCa-118b tumors and injected subcutaneously into SCID mice (1×10 6 cells per mouse). LDN193189 or vehicle is applied to mice 5 days post-tumor cell injection before tumors are palpable. The differences in the average growth rates between these two groups, as measured by tumor size, are significant at 6 and 7 weeks post-treatment. The tumor weights also show significant differences at the termination of the study at week 7. The X-ray of the tumors shows that the ectopic bone volume and bone density are reduced in the tumors of LDN193189-treated group compared to that of controls [2]. Co-incubation of pulmonary arterial smooth muscle cells (PASMCs) from the pulmonary arterial hypertension (PAH) rats with UK-92480 and LDN193189 completely inhibited the anti-proliferation and up-regulation of the bone morphogenetic protein (BMPR2) and Cx40 expression by the UK-92480 [3].

2310134-98-4

C25H26Cl4N6

552.33

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years