Investigation of the effect of potential Stathmin 1 inhibitors obtained by chemoinformatics on the phenotype of acute leukemias

• Grant number: 18/19372-9
• Support type: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2019
• Effective date (End): December 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: João Agostinho Machado Neto
• Grantee: Jorge Antonio Elias Godoy Carlos
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acute leukemias are aggressive neoplasias characterized by clonal proliferation with replacement and accumulation of neoplastic blasts in bone marrow or peripheral blood. Despite great advances in understanding the complexity behind the molecular changes in acute leukemia in recent years, very little has been translated into new therapies. Stathmin 1 is a microtubule destabilizing protein that integrates multiple signaling pathways, is highly expressed in leukemia cells (cell lines and primary cells) and plays a role relevant to the maintenance of the leukemia phenotype, including increased cell proliferation and clonogenicity. However, the translation of this knowledge obtained through genetic inhibition of Stathmin 1 (siRNA or shRNA) in pharmacological therapy, as well as the identification of selective inhibitors for Stathmin 1, still remain little explored. Thus, the objectives of this research project, using well established acute leukemia models, are: (i) to identify potential Stathmin 1 inhibitors by chemoinfomatics (ii) to test the effects of the selected compounds in relation to the Stathmin 1 activity and microtubule stability; (ii) evaluate the biological activity of the selected compounds in relation to cell viability, proliferation, clonogenicity, apoptosis, cell cycle progression; and related cell signaling pathways. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CARLOS, JORGE ANTONIO ELIAS GODOY; LIMA, KELI; COSTA-LOTUFO, LETICIA VERAS; LEITAO, ANDREI; MACHADO-NETO, JOAO AGOSTINHO. AD80, a multikinase inhibitor, exhibits antineoplastic effects in acute leukemia cellular models targeting the PI3K/STMN1 axis. INVESTIGATIONAL NEW DRUGS, v. 39, n. 4, p. 1139-1149, AUG 2021. Web of Science Citations: 0.

HIRAKATA, CAMILA; LIMA, KELI; DE ALMEIDA, BRUNA OLIVEIRA; DE MIRANDA, LIVIA BASSANI LINS; FLORENCIO, KATHARINE GURGEL DIAS; FURTADO, LUCIANA COSTA; COSTA-LOTUFO, LETICIA VERAS; MACHADO-NETO, JOAO AGOSTINHO. Targeting glioma cells by antineoplastic activity of reversine. Oncology Letters, v. 22, n. 2 AUG 2021. Web of Science Citations: 0.

ELIAS GODOY CARLOS, JORGE ANTONIO; LIMA, KELI; COELHO-SILVA, JUAN LUIZ; ALVES-PAIVA, RAQUEL DE MELO; MORENO, NATALIA CESTARI; VICARI, HUGO PASSOS; DE SOUZA SANTOS, FABIO PIRES; HAMERSCHLAK, NELSON; COSTA-LOTUFO, LETICIA VERAS; TRAINA, FABIOLA; MACHADO-NETO, JOAO AGOSTINHO. Reversine exerts cytotoxic effects through multiple cell death mechanisms in acute lymphoblastic leukemia. CELLULAR ONCOLOGY, v. 43, n. 6 AUG 2020. Web of Science Citations: 0.