FGFR1-BASED ANTAGONISTS WITH IMPROVED GLYCOSAMINOGLYCAN AFFINITY AND METHODS OF USING SAME

摘要

A novel approach for inhibiting FGF2/FGFR1 -mediated signalling is presented which is based on FGFR1 mutations to introduce higher affinity for the natural GAG co- receptors into the soluble part of the FGF1 receptor, preferably into the D2/D3 domains. Such recombinant drugs are expected to disrupt the natural FGF2/FGFR1/GAG triple complex by competing with the wtFGFR1 for GAG binding