生物活性

• 靶点

  ALK6 IC50:6.4nM

  ALK1 IC50:1.8nM

  ALK2 IC50:1.1nM

• 描述Bone morphogenetic proteins (BMPs), members of the TGFβ superfamily, play an important role in stem cell biology and function to regulate cell proliferation and differentiation during development. 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]. K02288 is a potent BMP type I receptor inhibitor with IC50s of 1.8, 1.1, 6.4 nM for ALK1, ALK2 and ALK6, respectively. K02288 also shows slightly weaker inhibition against ALK3 and ALK6 with IC50s of of 5-34 nM. Furthermore, K02288 further demonstrated an improved selectivity against ALK4 and ALK5 with IC50s of 321 nM and 302 nM, respectively. In C2C12 cells, the phosphorylation of Smad1/5/8, induced by BMP4, can be reduced by K02288 in a dose dependent manner with an apparent IC50 of 100 nM ^[4]. In LX-2 cells, the proliferation promotion effect of BMP9 stimulation was inhibited by incubating with 1μM of K02288 for 4 hours. In addition, the expression of pSMAD1/5, ID1, and α-SMA were significantly decreased by K02288 treatment^[5]. On embryo development day 6, 100μl of K02288 (1μM) was deposited on the chick embryo chorioallantoic membrane (CAM) model. Four days later, a large fraction of the CAM models exhibited a distinctive phenotype of low vessel density reflecting the dysfunctional angiogenesis which occurs following hypersprouting^[1].
• 作用机制K02288 binds type I BMP receptor at the ATP-binding pocket. The 2-aminopyridine group of K02288 is an ATP-mimetic that binds the kinase hinge region of type I BMP receptor through two conserved hydrogen bonds^[4].