title: SGI-110: DNA Methyltransferase Inhibitor Oncolytic.
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.
authors.affiliation: Roswell Park Cancer Institute, Elm & Carlton Sts., Buffalo, New York 14263, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Griffiths
authors.affiliation: Astex Pharmaceuticals, 4140 Dublin Blvd., Dublin, California 94582, USA.
authors.forename: G
authors.initials: G
authors.lastname: Choy
authors.affiliation: Astex Pharmaceuticals, 4140 Dublin Blvd., Dublin, California 94582, USA.
authors.forename: S
authors.initials: S
authors.lastname: Redkar
authors.affiliation: Astex Pharmaceuticals, 4140 Dublin Blvd., Dublin, California 94582, USA.
authors.forename: P
authors.initials: P
authors.lastname: Taverna
authors.affiliation: Astex Pharmaceuticals, 4140 Dublin Blvd., Dublin, California 94582, USA.
authors.forename: M
authors.initials: M
authors.lastname: Azab
authors.affiliation: University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Karpf
keywords: Acute myeloid leukemia; Hepatocellular carcinoma; Hypomethylating prodrug; Myelodysplastic syndrome; SGI-110; ovarian cancer