Potential multitarget inhibitor discovery for breast cancer (TNBC/IBC) from HDAC6 inhibitors: In silico approaches from experimental data

Year 2026, Volume: 10 Issue: 3, 71 - 90

Onur Ertik

Abstract

The incidence of breast cancer is increasing day by day due to genetic factors as well as lifestyle and diet. TNBC and IBC, which are particularly aggressive types of breast cancer, are among the breast cancer types with the highest metastasis ability. Moreover, due to the relationship between HDAC6 activity and TNBC and IBC breast cancer types, a multi-targeted approach for the discovery of drug molecules can be considered. In the present study, molecules with experimental HDAC6 inhibition and molecules with positive anticancer predictions on breast cancer were identified and 16 molecules with IC50 values lower than 25nM were identified. Then molecular docking studies of the 16 molecules for EGFR, HER2 and HER3 were performed. As a result of the evaluation of all results, it was found that compound C5 (N-[3-[[4-(4-acetamidophenyl)pyrimidin-2-yl]amino]phenyl]-N'-hydroxyhexanediamide) and C7 (N-hydroxy-5-[5-[1-[4-(trifluoromethyl)phenyl]-9H-pyrido[3,4-b]indol-3-yl]-1,3,4-oxadiazol-2-yl]pentanamide) had the best docking results for all target proteins. Molecular dynamics simulation results for compound C5, C7 and standard molecules showed that compound C7 was the best inhibitor candidate. The results suggest that compound C7 have a multi-targeted inhibitory effect and may be a drug candidate molecule for the treatment of TNBC and IBC breast cancer.

Keywords

Breast cancer , TNBC , in silico , drug , HDAC6

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