GEM144

GEM144 is a dual inhibitor of DNA polymerase alpha (POLA1) and histone deacetylase 11 (HDAC11). It inhibits the primer extension activity of POLA1 in a cell-free assay when used at concentrations ranging from 10 to 50 µM and increases acetylation of alpha-tubulin at lysine 40 in H460 lung cancer cells at 0.4 µM. It inhibits proliferation in a panel of cancer cell lines, including three malignant melanoma (IC50s = 0.73-1.4 µM), six hematological (IC50s = 0.16-3.2 µM), one breast cancer (IC50 = 0.77 µM), and one glioma cell line (IC50 = 1 µM). GEM144 (50 mg/kg) reduces tumor growth in an H460 mouse xenograft model and an MM487 orthotopic, malignant pleural mesothelioma xenograft model.. SMILES: CC(C(NO)=O)OC1=C(C=C(C(C=C2)=CC=C2/C=C/C(O)=O)C=C1)C3(C[C@H](C4)C5)CC5CC4C3. InChi Code: InChI=1S/C28H31NO5/c1-17(27(32)29-33)34-25-8-7-23(22-5-2-18(3-6-22)4-9-26(30)31)13-24(25)28-14-19-10-20(15-28)12-21(11-19)16-28/h2-9,13,17,19-21,33H,10-12,14-16H2,1H3,(H,29,32)(H,30,31)/b9-4+/t17?,19-,20?,21?,28?. InChi Key: PIJPEZHKJKJZHS-PMWLYXLASA-N