{Reference Type}: Journal Article
{Title}: Discovery of a dual-target DYRK2 and HDAC8 inhibitor for the treatment of hepatocellular carcinoma.
{Author}: Zhang L;Guan L;Wang Y;Niu MM;Yan J;
{Journal}: Biomed Pharmacother
{Volume}: 177
{Issue}: 0
{Year}: 2024 Aug 17
{Factor}: 7.419
{DOI}: 10.1016/j.biopha.2024.116839
{Abstract}: Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) and histone deacetylase 8 (HDAC8) have been shown to be associated with the development of several cancers. Here, we identified a dual-target DYRK2/HDAC8 inhibitor (DYC-1) through a combined virtual screening protocol. DYC-1 exhibited nanomolar inhibitory activity against both DYRK2 (IC50 = 5.27 ± 0.13 nM) and HDAC8 (IC50 = 8.06 ± 0.47 nM). Molecular dynamics simulations showed that DYC-1 had positive binding stability with DYRK2 and HDAC8. Importantly, the cytotoxicity assay indicated that DYC-1 exhibited superior antiproliferative activity against human liver cancer, especially SK-HEP-1 cells, and had no significant inhibition on normal liver cells. Moreover, DYC-1 showed a strong inhibitory effect on the growth of SK-HEP-1 xenograft tumors with no significant side effects. These data suggest that DYC-1 is a high-efficacy and low-toxic antitumor agent for the treatment of hepatocellular carcinoma.