Compound 54

Compound 54 is a novel acylureidoindolin-2-one derivative synthesized as a dual inhibitor of Aurora B and FLT3. It demonstrates potent cytotoxicity with single-digit nanomolar IC50 values against FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines, MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). The drug specifically induces extrinsic apoptosis by inhibiting the phosphorylation of both Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 has shown to be more potent than sunitinib against FLT3-WT AML cells and is also active against sunitinib-resistant FLT3-ITD AML cells. Its mesylate salt has effectively inhibited tumor growth and reduced mortality in BALB/c nude mice with subcutaneous xenografts of AML MOLM-13 cells.

Other names

(Z)-N-(2-(pyrrolidin-1-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyl)ureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide