Targeting the target: elucidating T44Bf mechanism of action, a lead compound identified from a phenotypic screening

FEDERICO REMES LENICOV; CARINA SHAYO; CARLOS DAVIO; NATALIA GÓMEZ; ANGELA RODRIGUEZ; NATALIA FERNANDEZ; MAIA CABRERA; EMILIANA ECHEVERRÍA; ALBERTINA MOGLIONI

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas; 2016

SAIC

Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified by phenotypic screening 4,4?-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines. Previous results indicate that T44Bf-mediated antiproliferative effects are associated with mitotic arrest, followed by programmed cell death. Since target deconvolution broadly improves drug discovery programs seeking to optimize and progress lead compounds obtained from phenotypic screening, the aim of this work was to delve into the mechanism of action of T44Bf that will allow its further rational optimization. Present findings indicate that T44Bf mitotic arrest is a reversible event as was evidenced by G0/G1 subpopulation levels reestablishment after two hours of T44Bf removal (p