生物活性

• 描述Colony-Stimulating-Factor Receptor-1 (CSF-1R) is a tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. CSF-1R promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. CSF-1R also promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. In response to ligand binding, CSF-1R activates several signaling pathways. Reports inferred that CSF-1R may be involved in cancer progression. Edicotinib, also termed JNJ-40346527, is a selective colony-stimulating factor-1 (CSF-1) receptor inhibitor. In lung cancer H1299 cells, edicotinib concentration dependently suppressed the level of Tyr ⁷²³, and the effect was obvious at the concentration of 250 nM. Edicotinib also concentration dependently inhibited the colony formation ability of lung cancer Calu-1, A549, H1975 and H1299 cell lines . In a subcutaneous C57BL6 mice model of lung carcinoma established by implantation of LLC cells, edicotinib was administered at dose 20 mg/kg 6 days per week p.o.. The results indicated that this dose and schedule of edicotinib in combination of CXCR2 antagonist SB225002 administered at dose 2mg/kg 6 days a week i.p. had significant anti-tumor activity. The same combination of these two drugs in a subcutaneous mice model of B16F10 melanoma was also efficient . According to another report, in a H1299 lung cancer xenograft established on NOD/SCID mice subcutaneously，treatment of edicotinib at the dose of 20 mg/kg by daily oral gavage for 16 days, in combination of cisplatin at the i.p. dose of 4 mg/kg once a week for 2 weeks had significant anti-tumor activity .

• 动物研究
  剂量	Mice: 5 mg/kg - 20 mg/kg[3] (p.o.), 3 mg/kg - 100 mg/kg[4] (p.o.)
  给药途径	p.o.