生物活性

• 描述Integrins are cell surface receptors involved in the integration between extracellular and intracellular signals in many biological processes, including cytoskeletal organization and cell adhesion, migration, proliferation, differentiation, and survival. During an immune response, integrins mediate cell adhesion to the extracellular matrix, and cell-cell interactions (e.g., T cell activation), which are central to the pathology of many inflammatory diseases, including dry eye disease (DED). Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1), thus interrupting the T cell-mediated inflammatory cycle. Lifitegrast demonstrated concentration-dependent inhibition of Jurkat cell attachment with an IC₅₀ value of 2.98 nM, suggesting it to be a potent antagonist of LFA-1/ICAM-1–mediated T-cell binding. Lifitegrast also demonstrated potent concentration-dependent inhibition of superantigen induced inflammatory cytokine release from human PBMCs, particularly the Th1 and Th2 T-cell cytokines, IFN-γ and IL-4, respectively. In normal healthy beagles, lifitegrast was well tolerated at concentrations as high as 10% with no apparent adverse effects on the cornea surface or overall ocular health.

• 动物研究
  剂量	Rat: 10 mg/kg[2] (i.v.)
  给药途径	i.v.
  动物药代数据	Animal Rats[2] Dose 10 mg/eye Administration i.v. T1/2β 36.2 h (male) 40.7 h (female) Vd 21.2 L/kg (male) 21.3 L/kg (female)