Naslov
Inhibitori histonskih deacetilaza kao protutumorski lijekovi
(Histone deacetylase inhibitors as antitumour drugs)

Autori
Poje, Goran ; Rajić, Zrinka

Izvornik
Farmaceutski glasnik : glasilo Hrvatskog farmaceutskog društva (0014-8202) 76 (2020), 4-5; 261-280

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, stručni

Ključne riječi
histonska deacetilaza ; citostatik ; inhibitor
(histone deacetylase ; cytostatic ; inhibitor)

Sažetak
Histone deacetylases (HDACs) catalyze the removal of the acetyl group from an ε-N-acetyl lysine on a histone, resulting in a more tight DNA structure. In this way, they affect chromatin structure and gene expression. They catalyze the same reaction on some non-histone proteins. Inhibition of overexpressed HDACs in tumour cells results in cell cycle arrest, induction of apoptosis, inhibition of angiogenesis and regulation of cellular signaling pathways in a survival-negative manner. Out of 4 known HDAC classes, classes I, II and IV are zinc-dependent enzymes, while class III is NAD+ dependent. All known HDACs inhibitors contain zinc-binding group, responsible for complexation of Zn2+ from the enzyme's active site. Other main structural features include cap group and the linker. With respect to the zinc- binding group, inhibitors can be divided into hydroxamic acids (the most pronounced ability to chelate Zn2+), carboxylic acids, cyclic peptides, and o-aminoanilides. Up to date, five HDACs inhibitors have reached the market: vorinostat, belinostat, and panobinostat (hydroxamic acids), romidepsin (cyclic peptide) and chidamide (o- aminoanilide). They are used in the therapy of T- cell lymphomas and multiple myeloma.

Izvorni jezik
Hrvatski

Znanstvena područja
Farmacija

POVEZANOST RADA