Patent ID: 8131527

Claim:
A method of identifying a compound which is a candidate modulator of fibroblast growth factor receptors (FGFR) having greater affinity for FGFR than for Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), the method comprising: (a) designing and/or selecting a candidate modulator using the pharmacophore represented by Formula 1: wherein Group D is a chemical group containing an unsaturated (pi) system in which at least two of the atoms in Group D form a double, triple or aromatic bond; and W is any atom, whether as an atom in a ring system or not; (b) generating on a computer a representation of said candidate modulator of step (a); (c) generating on a computer the atomic coordinates of a FGFR protein or a portion thereof having at least the binding pocket around Asp641 (according to 1AGW numbering); (d) fitting one or more candidate modulators according to step (b) to one or more FGFR residues to determine the probability of the candidate modulator interacting with FGFR, wherein the NH of Formula 1 forms a direct hydrogen bond with one or both of the Asp641 oxygens of the carboxylic acid; (e) optionally modifying said candidate modulator based on the result of the fitting step; (f) contacting said candidate modulator with FGFR and/or VEGFR2 to determine the ability of said candidate modulator to interact with FGFR and/or VEGFR2; and identifying a candidate modulator which is capable of binding or modulating FGFR, said candidate modulator having greater affinity for FGFR than for VEGFR2.