生物活性

• 靶点

  ALK1 IC50:2.4nM

  ALK3 IC50:85.8nM

  ALK2 IC50:1.3nM

• 描述The bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and in the normal and pathophysiologic remodeling of tissues. BMPs initiate their signaling events through an interaction of their type I and type II receptors, both of which are transmembrane serine/threonine kinases. Seven type I receptors (a.k.a. activin receptor-like receptors; ALK1 to ALK7) and four type II receptors have been identified in mice and humans^[3].. LDN-212854 is a selective and potent inhibitor of the BMP type I receptor kinases, with the IC50 values of 1.3 nM, 2.4 nM, 85.8 nM, 2133 nM, 9276 nM for ALK2, ALK1, ALK3, ALK4 and ALK5, respectively. LDN-212854 (IC50=37 nM) displayed low nanomolar potency in blocking the phosphorylation of SMAD1/5/8 induced by BMP7 (20 ng/mL, 30 min) in BMPR2^−/− pulmonary vascular smooth muscle cells. ALK2^Q207D transgenic mice model was used to evaluate the efficacy of LDN-212854 in vivo. After pretreating pericytes with 570nM LDN-212854 for 1 day, the osteoblast differentiation of pericytes from FOR hiPSCs was partly inhibited. Treatment with LDN-212854 on the dose of 6 mg/kg twice daily for 4 weeks can prevent the formation of heterotopic bone and preserved limb range of motion with minimal or no impairment in the majority of mice^[4].
• 作用机制LDN-212854 binds type I BMP receptor at the ATP-binding pocket. The pendant 5-quinoline group of LDN-212854 is predicted to form an alternative water-mediated hydrogen bond to the catalytic lysine (K235) of ALK2^[5].

• 动物研究
  剂量	Mice: 6 mg/kg[1] (i.p.)
  给药途径	i.p.