Starosyla S. Development of pharmacophore models and inhibitors of protein kinases ASK1, FGFR1 and CK2

The thesis is devoted to the development of pharmacophore models and low-molecular inhibitors for human protein kinases ASK1, FGFR1 and CK2 using methods of computer modeling and biochemical testing. Ligand-based pharmacophore model of ASK1 inhibitors was developed and validated in silico. Receptor-based pharmacophore models of FGFR1 and CK2 inhibitors were developed and experimentally validated. Six novel classes of inhibitors were identified: benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-ones - for ASK1, 2-(phenylamino)-5-(phenylmethylidene)-4,5-dihydro-1,3-thiazol-4-ones and tetrazolo[1,5-c]quinazolines - for CK2, 3-(1-benzyl-1H-indol-3-yl)-2-cyanoacrylic acids, N-[(phenylmethylidene)amino]thioureas, pyridine-3-carbonitriles - for FGFR1. The algorithm for pharmacophore model optimization and rescoring of pharmacophore screening results was developed.