MR22388, a novel anti-cancer agent with a strong FLT-3 ITD kinase affinity.

Christophe Rochais (1) , Thierry Cresteil (2) , Vittoria Perri (1) , Marie Jouanne (1) , Aurélien Lesnard (1) , Sylvain Rault (1) , Patrick Dallemagne (1)

1 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie
2 ICSN - Institut de Chimie des Substances Naturelles

This work describes the study of the mechanism of action and spectrum of activity of MR22388, a novel anti-cancer agent belonging to the tripentone series. MR22388 is highly cytotoxic (within the nanomolar range) against numerous cancer cell lines and studies of its cytotoxicity mechanisms show that it is a weak inhibitor of the polymerization of tubulin and that it induces apoptosis via the MAP kinase pathways. Further MR22388 is a very strong inhibitor of several kinases including the tyrosine kinase FLT3-ITD. FLT3-ITD is a mutated form of the tyrosine kinase receptor (RTK) FLT3, resulting in the constitutive activation of the kinase, occurring in about 25% of normal karyotypes' Acute Myeloid Leukemia (AML) and is linked to a bad prognosis. Consecutively, MR22388 appears as a novel promising anticancer lead agent especially for AML therapy.

Domaines: Chimie organique

Christophe Rochais, Thierry Cresteil, Vittoria Perri, Marie Jouanne, Aurélien Lesnard, et al.. MR22388, a novel anti-cancer agent with a strong FLT-3 ITD kinase affinity.. Cancer Letters, 2013, 331 (1), pp.92-8. ⟨10.1016/j.canlet.2012.12.017⟩. ⟨hal-00807871⟩