RUNX1/CBFβ inhibitor

Background

Coe-binding transcription factors (CBFβ have roles in stem cell self-renewal, tissue differentiation and cancer. They are heterodimeric complexes consisting of two subunits, α and β, in which α subunit binds to DNA, while β subunit is thought to stabilize the DNA binding of α subunit. RUNX1 (also called AML1) is the CBFβsubunit which is predominantly expressed during hematopoietic development.

Concept

RUNX1 and CBFβare frequently involved in chromosomal alterations associated with hematopoietic diseases, for example, in t(8;21) and inv(16) acute myeloid leukemia (AML). The translocation involving chromosomes 8 and 21 fuses the RUNX1 and ETO genes, leading to the expression of AML1-ETO. Expression of AML1-ETO oncofusion protein in hematopoietic cells results in a stage-specific arrest of maturation and increased cell survival, predisponsing cell to develop leukemia. We therefore planned to develop RUNX1/CBFβ inhibitors as anti-AML therapy.