QC6352

QC6352 is an orally active KDM4 inhibitor with anti-tumor and anti-proliferative activity. QC6352 has in vivo inhibitory effects on PDX models of breast and colon cancer and reduces the number of chemoresistant cell populations. QC6352 inhibits KDM4 different isoforms with IC₅₀s of 104 nM (KDM4A), 56 nM (KDM4B), 35 nM (KDM4C), and 104 nM (KDM4D), respectively. QC6352 has moderate inhibitory activity against KDM5 with an IC₅₀ of 750 nM (KDM5B)^[1][2]. IC50 & Target:IC50: 104 nM (KDM4A), 56 nM (KDM4B), 35 nM (KDM4C), 104 nM (KDM4D), 750 nM (KDM5B)^[2] In Vitro:QC6352 is a potent KDM4C inhibitor with an IC₅₀ of 35±8 nM^[1]. In a concentration-dependent manner QC6352 dramatically reduces the sphere-forming capacity of BCSC1 and BCSC2. QC6352 blocks proliferation and self-renewal of BCSCs. As shown by western blot analysis the protein levels of (Epidermal growth factor receptor) EGFR are reduced in both BCSC1 and BCSC2 upon treatment with QC6352^[2]. In Vivo:QC6352 strongly affects tumor growth and final tumor weight of both BCSC1 and BCSC2 xenografts. Treatment with QC6352 is well tolerated and does not affect body weight of the mice. Results demonstrate that treatment with the KDM4 inhibitor QC6352 blocks BCSC xenograft tumor growth^[2].