The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia

Patients with AML harboring constitutively active mutations in the FLT3 receptor generally have a poor prognosis (FLT3-ITDMUT). Despite the fact that several FLT3 inhibitors have been developed, clinical responses are commonly partial or not durable, highlighting the need for new molecules targeting...

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Detalles Bibliográficos
Autores: López Millán, Belén, Costales, Paula, Gutiérrez Agüera, Francisco, Díaz de la Guardia, Rafael, Roca Ho, Heleia, Vinyoles, Meritxell, Rubio Gayarre, Alba, Safi, Rémi, Castaño, Julio, Romecín, Paola Alejandra, Ramirez Orellana, Manuel, Anguita Mandly, Eduardo Luis, Jeremías, Irmela, Zamora, Lurdes, Rodríguez Manzaneque, Juan Carlos, Bueno, Clara, Morís, Francisco, Menéndez, Pablo
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/71621
Acceso en línea:https://hdl.handle.net/20.500.14352/71621
Access Level:acceso abierto
Palabra clave:AML
EC-70124 multi-kinase inhibitor
FLT3-ITD mutation
FLT3 inhibitor
AML preclinical model
Oncología
3201.01 Oncología
Descripción
Sumario:Patients with AML harboring constitutively active mutations in the FLT3 receptor generally have a poor prognosis (FLT3-ITDMUT). Despite the fact that several FLT3 inhibitors have been developed, clinical responses are commonly partial or not durable, highlighting the need for new molecules targeting FLT3-ITDMUT. Here, we tested EC-70124, a hybrid indolocarbazole analog from the same chemical space as midostaurin (a well-known FLT3 inhibitor). Our in vitro and in vivo experiments showed that EC-70124 exerts a robust and specific antileukemia activity against FLT3-ITDMUT AML cells while sparing healthy hematopoietic cells. Collectively, EC-70124 is a promising and safe agent for the treatment of this aggressive type of AML.