text: 3-Hydroxypyridin-2-thione as Novel Zinc Binding Group for Selective Histone Deacetylase Inhibition.
  Small molecules bearing hydroxamic acid as the zinc binding group (ZBG) have been the most effective histone deacetylase inhibitors (HDACi) to date. However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety have stimulated research efforts aimed at finding alternative nonhydroxamate ZBGs. We have identified 3-hydroxypyridin-2-thione (3-HPT) as a novel ZBG that is compatible with HDAC inhibition. 3-HPT inhibits HDAC 6 and HDAC 8 with an IC50 of 681 and 3675 nM, respectively. Remarkably, 3-HPT gives no inhibition of HDAC 1. Subsequent optimization led to several novel 3HPT-based HDACi that are selective for HDAC 6 and HDAC 8. Furthermore, a subset of these inhibitors induces apoptosis in various cancer cell lines.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: histone deacetylase HDAC HDAC HDAC 6 HDAC 8 HDAC 1 HDAC HDAC 6 HDAC 8 Histone Deacetylase hydroxamic acid 3-hydroxypyridin-2-thione 3-HPT 3-HPT zinc 3-HPT 3HPT 3-Hydroxypyridin-2-thione Zinc