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Information × Registration Number 0223U004538, 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 16-11-2023 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description2 In the course of the work, structure-activity relationships determining the antitumor activity of novel dual inhibitors of casein kinase 2 and histone deacetylase were clarified. It was shown that pro-apoptotic activity of these compounds depends on the presence of a tertiary amine atom in DMAT-benzamide derivatives and on the length of the aliphatic chain in DMAT-hydroxamate derivatives. Important role of oxidative stress in overcoming the acquired cancer drug resistance by novel dual kinase inhibitors was also demonstrated. Based on the results of in vitro experiments performed by us at the 1st stage of this project in 2021, 2nd generation of dual kinase inhibitors with activity in the nanomolar range were synthesized by Spanish collaborators. We did not find negative effect of these compounds IOR-180 and IOR-140 on the functioning of hematopoietic system, kidneys and liver of healthy mice at a dose of 16 mg/kg both on the 30th day and on the 75th day after last administration of these compounds. IOR-180 was shown to be a potent inducer of immunogenic cell death, 100% protecting animals against re-inoculation of B16 melanoma, while this index was 90% for doxorubicin, 60% for CX-4945 (clinically available SC2 inhibitor), and only 40% for oxaliplatin. The obtained results indicate on significant prospects for the use of IOR-180 as part of combined chemotherapy regimens to enhance the action of traditional drugs by potent induction of IPC in tumor cells. Using recombinant (His)6-tagged creatinine deaminase (KDI), three types of amperometric biosensors were developed for determining creatinine content, of which the sensor based on Cu/Zn(Hg)S was characterized by the highest selectivity and sensitivity to creatinine (2600 ± 101 А∙M- 1∙m-2) in the range from 1.5 μM to 50 μM with a lower limit of creatinine determination of 0.45 μM. The developed biosensors based on recombinant KDI have been successfully tested for the analysis of creatinine in real blood serum samples. Product Description popup.authors Ivasechko Iryna Igorivna Kozak Yuliia S. Stasyuk Nataliya Yevgenivna popup.nrat_date 2023-11-16 Close