3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 587-590)
АУТОР(И) / AUTHOR(S): Aleksandra Ilić, Milan Beljkaš, Alen Čebzan, Branko Radović, Nemanja Djoković, Katarina Nikolić, Slavica Oljačić
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DOI: 10.46793/ICCBIKG25.587I
САЖЕТАК / ABSTRACT:
Histone deacetylases (HDACs) are epigenetic regulators involved in cancer development. Although several non-selective HDAC inhibitors have been approved, their clinical use is limited by toxicity and off-target effects. To improve selectivity and efficacy, newer strategies focus on dual-target inhibitors that modulate other cancer-related signaling pathways in addition to HDACs. In this study, structure-based modeling and docking were used to develop novel dual inhibitors targeting HDAC6 or sirtuin2 (SIRT2) in combination with Aurora kinase A (AURKA), glutaminase (GLS) or WEE1 kinase, guided by pharmacophore models. The developed compounds showed strong predicted binding and favorable ADMET profiles. We present nine promising dual inhibitors for HDAC6/WEE1, HDAC6/GLS1 and SIRT2/AURKA with improved or comparable properties to the reference ligands.
КЉУЧНЕ РЕЧИ / KEYWORDS:
histone deacetylases inhibitors; cancer; dual-target therapy; rational design
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This research was funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia through two Grant Agreements with University of Belgrade-Faculty of Pharmacy No 451-03-136/2025-03/ 200161and No 451-03-137/2025- 03/ 200161. The authors thank the COST Actions CA22125 and CA23111 of the European Community for support.
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