Synthesis and evaluation of 2,5-substituted pyrimidines as small-molecule gankyrin binders.

Gankyrin is an ankyrin-repeat protein that promotes cell proliferation, tumor development and cancer progression when overexpressed. To design and synthesize a novel series of gankyrin-binding small molecules predicated on a 2,5-pyrimidine scaffold. The synthesized compounds were evaluated for their antiproliferative activity, ability to bind gankyrin and effects on cell cycle progression and the proteasomal degradation pathway.