ZLD1039 potent, highly selective, and orally bioavailable small molecule inhibitor of EZH2, which inhibited the methyltransferase activity of EZH2 with high selectivity across an HMT panel. Treatment of xenograft-bearing mice with ZLD1039 led to tumor growth regression and metastasis inhibition, confirmed the dependency of breast cancer progression on EZH2 activity and the usefulness of ZLD1039 as a promising treatment for breast cancer.