生物活性

• 靶点	Mer IC50:1.7nM

• 描述Mer belongs to the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (RTK). This subfamily of RTKs transduce signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Abnormal activation or overexpression of Mer RTK has been implicated in neoplastic progression of many human cancers and has been correlated with poorer prognosis. UNC2250 is a Mer kinase inhibitor which achieved selectivity against the other two members of Tyro3 and Axl. Based on a microfluidic capillary electrophoresis assay, the IC50 of UNC2250 against Mer was 1.7 nM, while the IC50s against Axl and Tyro3 were 270 nM and 100 nM, respectively . UNC2250 inhibited Mer phosphorylation with the IC50 value of 9.8 nM as detected by western blotting. In soft agar colony formation assays, UNC2250 inhibited colony formation of the BT-12 rhabdoid tumor and the NSCLC Colo699 cells. According to another report, UNC2250 inhibited proliferation of the mantle cell lymphoma cell lines Z-138, Mino, and JVM-13 with IC50 values of 3.0 μM, 3.1 μM and 7.7 μM, respectively. In an apoptosis assay, flow cytometry analysis revealed that 4 μM UNC2250 induced apoptosis in Z-138 cells by 45.2% and Mino cells by 44.4% post 12h treatment, and when the time was extended to 24 or 48h, the apoptosis rates induced by 4 μM UNC2250 increased to 76.9 or 98.0% in Z-138 cells and to 81.5 or 98.1% in Mino cells. In an mantle cell lymphoma Z-138 xenograft model established on NOD/SCID mice, UNC2250 was administrated once daily by oral gavage for 10 days. UNC2250 produced significant anti-tumor effects on tumor volume at the doses of 50 and 75 mg/kg. The tumor inhibition rates were 35 and 48%, respectively.

• 动物研究
  剂量	Mouse: 3 mg/kg[2] (i.v.); 25 mg/kg - 75 mg/kg[3] (p.o., qd)
  给药途径	i.v., p.o.