While KDM5B and its inhibitors likely regulate other targets, our studies are the first to show that induction of HEXIM1 expression is required for ability of KDM5B inhibitors to (1) induce p21 expression and differentiation, (2) inhibit expression of oncogenic genes such as cyclin D1 and Myc, and (3) inhibit breast cancer cell proliferation. Here, MYC is linked to breast carcinoma.