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Information × Registration Number 0222U004459, 0121U110732 , R & D reports Title Novel dual inhibitors of casein kinase 2 and histone deacetylase for targeted tumor chemotherapy popup.stage_title Head Panchuk Rostyslav R., Доктор біологічних наук Registration Date 08-08-2022 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description2 Extremely high price and short-term therapeutic effect due to the rapid development of cancer drug resistance are considered the main disadvantages of modern targeted cancer therapy. We have proposed an alternative approach to solve this problem, which is based on the combination of pharmacophores of inhibitors of several structurally and functionally different protein kinases in one molecule. In the course of the work, study of the molecular mechanisms of antitumor activity of 6 different representatives of dual kinase inhibitors was carried out in vitro, which allowed us to identify structure-activity relationships underlying their antineoplastic potential. It was demonstrated for the first time that the pro-apoptotic activity of these compounds depends on the presence of a tertiary amine atom in DMAT-benzamide derivatives and the length of the aliphatic chain in DMAT and hydroxamate derivatives. Increasing the number of methyl groups from 5 to 7 doubled the cytotoxic and pro-apoptotic activity of the above-mentioned inhibitors. Additionally, we have demonstrated an important role of oxidative stress in circumvention of cancer drug resistance by novel dual inhibitors of casein kinase 2 and histone deacetylase. Product Description popup.authors Ivasechko Iryna Igorivna Kozak Yuliia S. Skorokhyd Nadiya R. Stasiuk Nataliia Ye. popup.nrat_date 2022-08-08 Close