Разработка ингибиторов фермента репарации ДНК тирозил-ДНК- фосфодиэстеразы1 и его природного мутанта Scan1 в качестве прототипов лекарственных препаратов

Abstract

In the present study, we performed screening of 21 compounds - derivatives of coumarin as inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1) and its mutant SCAN1. The ability of these compounds to inhibit Tdp1, important target for anti-cancer therapy, was studied. The most active derivatives have IC50 value of 0,1-1 mkM. SCAN1 inhibitors were found first in the world. They can likely underlie the development of drugs preventing or slowing the progressive cerebellar atrophy to improve quality of life of SCAN patients.