rg7388 and Leukemia--Prolymphocytic--T-Cell

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where

Topics: Animals; Antineoplastic Agents; Apoptosis; Bendamustine Hydrochloride; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Drug Synergism; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Leukemia, Prolymphocytic, T-Cell; Male; Mice; Molecular Docking Simulation; Molecular Structure; para-Aminobenzoates; Pyrrolidines; Structure-Activity Relationship; Sulfonamides