CADD522 is an inhibitor of RUNX family transcription factor 2 (RUNX2) binding to DNA.1 It inhibits RUNX2 binding to osteoblast-specific element 2 (OSE2) oligonucleotides in a cell-free assay, as well as inhibits RUNX2 enrichment on matrix metalloproteinase-13 (MMP-13) promoters in MCF-7 cells when used at concentrations ranging from 100 to 1,000 nM. CADD522 (50 ?M) decreases clonogenic survival in a panel of nine breast cancer cell lines. It decreases the expression of the RUNX2 target genes and metastasis markers MMP-13 and VEGF in ectopic RUNX2-expressing T47D-RUNX2 and MCF-7-RUNX2 breast cancer cells. CADD522 (20 mg/kg, i.p.) reduces tumor volume and incidence in the MMTV-PyMT transgenic mouse model of breast cancer.
1.Kim, M.S., Gernapudi, R., Choi, E.Y., et al.Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and exhibits antitumor activityOncotarget.8(41)70916-70940(2017)