LDN-193189 HCl (LDN193189 Hydrochloride) is a selective BMP type I receptor kinases inhibitor.

ALK6:16.7 nM, ALK1:0.8 nM, ALK2:0.8nM, ALK3:5.3nM

LDN193189有效抑制BMP4介导的Smad1、Smad5和Smad8激活，IC50为5 nM，同时高效抑制BMP型I受体ALK2和ALK3的转录活动，其IC50分别为5 nM和30 nM。此外，LDN193189亦对由ALK2R206H或ALK2Q207D突变蛋白质引起的转录活动显示出抑制效果。[1] 最近的研究显示，LDN-193189能阻断氧化LDL在动脉粥样硬化过程中引起的人类主动脉内皮细胞中活性氧物种的产生。[4]

在条件性caALK2转基因小鼠中，LDN-193189（3 mg/kg i.p）首次在P13时引起左侧胫骨和腓骨周围出现轻微的钙化，到P15则阻止了放射性病变的出现，且不引起体重减轻、生长迟缓、自发性骨折、骨密度降低或行为异常。[1] LDN193189通过抑制由骨形态发生蛋白（BMP）6激发的信号通路，使斑马鱼胚胎背化，但对血管发育无影响。[2] 在携带PCa-118b肿瘤的小鼠中，LDN-193189的治疗减缓了肿瘤生长并减少了肿瘤中的骨形成。[3] 在低密度脂蛋白受体缺失（LDLR-/-）的小鼠中，LDN-193189强效抑制了动脉粥样硬化斑块的发展。此外，LDN-193189还展现出对相关血管炎症、成骨活性及钙化的抑制作用。[4]

C2C12 cells are seeded into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. The wells are treated in quadruplicate with BMP ligands and LDN-193189 or vehicle. The cells are collected after 6 d in culture in 50 μL Tris-buffered saline and 1% Triton X-100. The lysates are added to p-nitro-phenylphosphate reagent in 96-well plates for 1 h and then evaluated alkaline phosphatase activity (absorbance at 405 nm). Cell viability are measured and quantity by Cell Titer Aqueous One (absorbance at 490 nm), using replicate wells treated identically to those used for alkaline phosphatase measurements[1].

Concentrations: 3 μM