Přehled

Topic:

Design, Synthesis and In Vitro Evaluation of Inhibitors of Mitochondrial Enzyme Cyclophilin D

Annotation:

Cyclophilin D (CypD) is a mitochondrial enzyme that regulates opening of the mitochondrial permeability transition pore (mPTP). Excessive mPTP opening is manifested in several diseases associated with mitochondrial dysfunction including ischemia-reperfusion injury or neurodegeneration. Suppression of mPTP opening through CypD inhibition represents a promising approach for treatment of above-mentioned diseases. However, only limited number of CypD inhibitors are currently available – mostly macrocyclic compounds derived from cyclosporin A, which suffer from undesirable physico-chemical properties and low selectivity for CypD over other cyclophilins. Thus, development of novel inhibitors with improved activity, selectivity and physico-chemical properties is a crucial issue to date.

Literature:

Haleckova, A.; Benek, O.; Zemanová, L.; Dolezal, R.; Musilek, K. Small-Molecule Inhibitors of Cyclophilin D as Potential Therapeutics in Mitochondria-Related Diseases. Medicinal Research Reviews 2022, vol. 42, no. 5, p. 1822–1855. DOI: 10.1002/med.21892

Supervisor: Kamil Musilek (https://www.uhk.cz/cs/osoba/4327/kamil-musilek)

Consultant: Ondrej Benek (https://www.uhk.cz/cs/osoba/295/ondrej-benek)