Ro 5-3335

Ro5-3335, a benzodiazepine, acts as an inhibitor of core binding factor (CBF) leukemia. Ro5-3335 is a RUNX1-CBFβ interaction inhibitor that represses RUNX1/CBFB-dependent transactivation[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

RUNX1-CBFβ interaction[1]

Ro5-3335 has antiproliferative activity against human CBF leukemia cell lines, with IC50s of 1.1 μM, 21.7 μM and 17.3 μM for ME-1, Kasumi-1 and REH, respectively[1]. Ro5-3335 inhibits definitive hematopoiesis in zebrafish embryos[1]. Ro5-3335 does not completely break apart RUNX1-CBFβ interaction, but changes the conformation of their complex or increases the distance between RUNX1 and CBFβ in the complex[1].

Ro5-3335 is identified as an inhibitor of RUNX1–CBFβ function in zebrafish models[1]. Ro5-3335 rescues preleukemic phenotype in a RUNX1-ETO transgenic zebrafish[1]. Ro5-3335 (300 mg/kg/d; p.o; for 30 days) reduces leukemia burden in a mouse CBFB-MYH11 leukemia model[1]. Animal Model: C57BL/6 mice (leukemic model)[1] Dosage: 300 mg/kg Administration: Oral administration; daily; for 30 days Result: Reduced the number of c-kit+ cells in the transplanted mice and leukemic cell infiltration in the livers, bone marrow and spleen.

[1]. Cunningham L, et al. Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14592-7.