QC6352

A KDM4 inhibitor, selective for KDM4A, KDM4B, KDM4C, and KDM4D (IC50s = 104, 56, 35, and 104 nM, respectively) over KDM2B, KDM3A, KDM3B, KDM6B, and PHF8 (IC50s = >4,000 nM for all) but does inhibit KDM5B (IC50 = 750 nM), increases H3K36Me3 levels in KYSE-150 cells (EC50 = 1.3 nM), reduces the proliferation of KYSE-150 cells (EC50 = 3.5 nM) but not IMR-90 fibroblasts (IC50 = >30 µM), reduces tumor volume in a BR0859f PDX mouse model of HER2-positive breast cancer at 10, 25, and 50 mg/kg. Formulation: A solid. InChI: InChI=1S/C24H25N3O2/c1-27(19-8-3-2-4-9-19)20-10-11-21-17(14-20)6-5-7-18(21)15-26-23-16-25-13-12-22(23)24(28)29/h2-4,8-14,16,18,26H,5-7,15H2,1H3,(H,28,29)/t18-/m0/s1. InChIKey: XSMABFRQESMONQ-SFHVURJKSA-N. SMILES: O=C(O)C1=CC=NC=C1NC[C@@H]2CCCC3=C2C=CC(N(C4=CC=CC=C4)C)=C3