TARGETING THE TARGET: ELUCIDATING T44BF MECHANISM OF ACTION, A LEAD COMPOUND IDENTI- FIED FROM A PHENOTYPIC SCREENING.

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

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Focusing on the extensively studied family of thiosemicarba-zone (TSC) compounds, we have previously identified by pheno-typic screening 4,4?-dimethoxybenzophenone thiosemicarbazone(T44Bf) as a promising pharmacological compound in a panel ofhuman leukemia cell lines. Previous results indicate that T44Bf-mediated antiproliferative effects are associated with mitotic arrest,followed by programmed cell death. Since target deconvolutionbroadly improves drug discovery programs seeking to optimize andprogress lead compounds obtained from phenotypic screening, theaim of this work was to delve into the mechanism of action of T44Bfthat will allow its further rational optimization. Present findings indicatethat T44Bf mitotic arrest is a reversible event as was evidenced byG0/G1 subpopulation levels reestablishment after two hours of T44Bfremoval (p