生物活性

• 靶点

  ALK1 IC50:27nM

  ALK2 IC50:107.9nM

  ALK3 IC50:5nM

• 描述BMPs (Bone morphogenetic proteins) represent the largest subgroup in the TGFβ family of extracellular ligands. Their signaling transduction requires the interaction with the type I and type II transmembrane receptor kinase. Type I receptors, such as ALK1/ACVRL1, ALK2/ACVR1, ALK3/BMPR1A and ALK6/BMPR1B all participate in BMP signaling and phosphorylate SMAD1/5/ 8 of SMAD family transcription factors^[2]. DMH-1 is a selective inhibitor of BMP type I receptors with IC50 values of 107.9 nM for ALK2 and with no activity on ALK5, AMPK, VEGFR2 or PDGFRβ (measured by in vitro kinase assays). DMH1 on concentration of 1-20 μM blocked BMP4-induced Smad 1/5/8 phosphorylation dose-dependently in HEK293 cells. In contrast, DMH1 had no effect on BMP4-induced p38 MAPK phosphorylation or Activin A-induced Smad2 phosphorylation^[1]. Mice expressing MMTV.PyVmT, with six-week pumps containing 7 mg DMH1, showed reduced lung metastasis and the tumors were less proliferative and more apoptotic compared with the control group^[3]. DMH1 is also used in cell differentiation or reprogramming, for example: 1.Combined with SB431542, DMH1 can induce neuralization of hiPSCs^[4]. 2. DMH1 can increase cardiomyocyte progenitors and promote cardiac differentiation in mouse embryonic stem cells^[5].
• 作用机制DMH-1 targets to the ATP-binding pocket located within the intracellular kinase domain of the receptors.^[6]

• 动物研究
  剂量	Mice[7] (i.p.): 5 mg/kg
  给药途径	i.p.