| Call | Mutual fund Taiwan – Latvia – Lithuania, 2019 |
| Implementation period | 01.01.2020. – 30.12.2022. |
| Project partners | National Central University, Taiwan Latvian Institute of Organic Synthesis, Latvia Vilnius University, Lithuania |
| Leader of the Latvian team | Dr. chem. Kirills Šubins |
| Total costs | 202 500 EUR |
| Costs for Latvian partner | 67 500 EUR |
Summary
The objective of this project is to perform preclinical development of an inhibitor designed as an anticancer drug for the treatment of triple-negative breast and highly invasive pancreatic cancers. Combined efforts of the three teams in Latvia, Lithuania and Taiwan should yield an inhibitor with an improved affinity towards CA IX and also improved selectivity over vital CAs in the human body to avoid toxic side effects of the compound. The lead compound is planned to be developed in GLP conditions with the help of Taiwanese CRO companies towards an anticancer drug. Taiwanese team will search for Institution for PMDK and toxicological studies mainly for pre-GLP experiments, make contact and propose joint development of the lead compound. Also, the Taiwanese team will measure by ITC the binding of sulfonamide inhibitors and carbonic anhydrases. Structure-thermodynamics correlations will be analyzed and all data will be used for further improvement of the drug design. Latvian team will synthesize, purify and characterize novel CA IX inhibitors containing different conjugated bulky groups. Results of ITC binding analysis will be used to guide further optimization of chemical structure. Lithuanian team will recombinantly clone, express in bacterial or mammalian cells and purify CA IX and other CA proteins. Together with compounds synthesized by Latvian team they will be used for measuring of Gibbs free energy of binding by fluorescent thermal shift assay. All three teams will analyze and summarize the data on the recognition energetics and the structure-activity relationships for the compound–target interaction for the several metallo-protein groups.