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Investigational New Drugs

Investigational New Drugs

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AD80, a multikinase inhibitor, exhibits antineoplastic effects in acute leukemia cellular models targeting the PI3K/STMN1 axis.

Published:1 August 2021 DOI: 10.1007/s10637-021-01066-w PMID: 33475938
Jorge Antonio Elias Godoy Carlos, Keli Lima, Leticia Veras Costa-Lotufo, Andrei Leit?o, Jo?o Agostinho Machado-Neto

Abstract

Despite the great advances in the understanding of the molecular basis of acute leukemia, very little of this knowledge has been translated into new therapies. Stathmin 1 (STMN1), a phosphoprotein that regulates microtubules dynamics, is highly expressed in acute leukemia cells and promotes cell cycle progression and proliferation. GDP366 has been described as a STMN1 and survivin inhibitor in solid tumors. This study identified structural GDP366 analogs and the cellular and molecular mechanisms underlying their suppressive effects on acute leukemia cellular models. STMN1 mRNA levels were higher in AML and ALL patients, independent of risk stratification (all p?

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