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

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.

► MR22388 is a novel anticancer agent belonging to the tripentones series.
► MR22388 is highly cytotoxic (within the nanomolar range) against numerous cancer cell lines.
► The activity of MR22388 is directed towards multiple targets involving both tubulin and kinase.
► The affinity of MR22388 is very selectively directed towards FLT3-ITD.
► AML cells expressing FLT3-ITD appear more sensible to the cytotoxic effect of MR22388.