Recently, the topic of covalent inhibitors has experienced a revival. About 50 covalent drugs have been approved by the US Food and Drug Administration, and many candidates have been selected for clinical trials. Target-specific covalent inhibitors exhibit significantly higher affinity and selectivity for the target enzyme isoform than inhibitors that reversibly bind to the target protein. Covalent inhibitors have prolonged therapeutic effects. They can overcome resistance mechanisms.
This doctoral study project aims to develop effective and selective target-specific covalent inhibitors for two proteins related to cancer development-carbonic anhydrase (CA)IX and histone deacetylase (HDAC)8. The human body contains 12 catalytically active CA isoforms performing vital functions in all tissues. CAIX is highly overexpressed in most cancer tissues but practically undetectable in healthy tissues. Selective inhibition of CAIX would prevent side effects and slow down the spread of cancer. HDACs are essential in cancer development. Although HDAC inhibitor drugs exhibit potent effects, adverse effects and toxicity occur due to non-selective inhibition of various HDAC isoforms. The structure of the active center of HDAC8 and the deacetylation substrates make this protein unique among 12 structurally and functionally related HDAC isoforms, and the goal is to develop a selective inhibitor of this protein.
Mokslinis vadovas / Supervisor: dr. Edita Čapkauskaitė
Kontaktai / Contacts:
tel. / phone: +37067796863
Programme: Chemistry engineering (Biotechnology) T 005