Characteristics and thermodynamics of the interaction of 6-shogaol with human serum albumin as studied by isothermal titration calorimetry

ABSTRACT The interaction between 6-shogaol, a pharmacologically active ginger constituent, and human serum albumin (HSA), the main in vivo drug transporter, was investigated using isothermal titration calorimetry (ITC). The value of the binding constant, Ka (5.02 ± 1.37 × 104 M−1) obtained for the 6-shogaol-HSA system suggested intermediate affinity. Analysis of the ITC data revealed feasibility of the binding reaction due to favorable enthalpy and entropy changes. The values of the thermodynamic parameters suggested involvement of van der Waals forces, hydrogen bonds and hydrophobic interactions in the 6-shogaol-HSA complex formation.

Development and ligand-protein interaction of small molecule anti-tumor FGFR inhibitors / 药学学报

Fibroblast growth factor receptors (FGFRs) are in the superfamily of receptor tyrosine kinases' (RTKs). Fibroblast growth factors (FGFs) bind to FGFRs with high-affinity, involving in many biological processes, such as the regulation of organ development, angiogenesis, cell proliferation, migration and anti-apoptosis. The activating mutations and amplification of the FGFR gene, resulting in FGFR protein amplification, are closely associated with the development and progression of many malignancies in human. In recent years, various small molecule FGFR inhibitors with different chemical backbones are designed, synthesized, and mainly applied to the clinical anti-cancer research. This article is devoted to review of selective second generation of small molecule FGFR inhibitors that are currently used in clinical trials, and the interaction with the FGFR protein, in order to provide strategies to the design of small molecule FGFR inhibitors.