Author/Authors :
Chia-Yu Huang، نويسنده , , Tara M. Stauffer، نويسنده , , Corey L. Strickland، نويسنده , , John C. Reader، نويسنده , , He Huang، نويسنده , , Ge Li، نويسنده , , Alan B. Cooper، نويسنده , , Ronald J. Doll، نويسنده , , Ashit K. Ganguly، نويسنده , , John J. Baldwin، نويسنده , , Laura L. Rokosz، نويسنده ,
Abstract :
Farnesyltransferase inhibitors identified from an ECLiPS® library were optimized using solution-phase synthesis. X-ray crystallography of inhibited complexes was used to identify substructures that coordinate to the active site zinc. The X-ray structures were ultimately used to guide the design of second-generation analogs with FTase IC50s of less than 1.0 nM.
Keywords :
anti-cancer , farnesyltransferase , rational drug design , Catalytic zinc , X-ray crystallography , Solution-phase synthesis
