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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
SGI-110: DNA Methyltransferase Inhibitor Oncolytic
E A Griffiths1, G Choy2, S Redkar2
1Roswell Park Cancer Institute, Elm & Carlton Sts., Buffalo, New York 14263, USA.
Abstract:
SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. This novel compound is an oligonucleotide consisting of decitabine linked through a phosphodiester bond to the endogenous nucleoside deoxyguanosine. The dinucleotide configuration provides protection from drug clearance by deamination, while maintaining at least equivalent effects on gene-specific and global hypomethylation both in vitro and in animal model systems. This agent is currently being tested in phase I and II clinical trials in humans and has been demonstrated to be safe and well tolerated as a single agent, with evidence of promising activity in heavily pretreated (including currently FDA approved hypomethylating drugs) myelodysplastic syndrome and acute myeloid leukemia patients. Ongoing trials are also open in platinum-resistant ovarian cancer and hepatocellular carcinoma.
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