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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.

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|July 21, 2015
PubMed
Summary
This summary is machine-generated.

SGI-110, a novel hypomethylating prodrug, shows promising safety and efficacy in clinical trials for myelodysplastic syndrome and acute myeloid leukemia. Its unique dinucleotide structure enhances stability and maintains therapeutic effects.

Keywords:
Acute myeloid leukemiaHepatocellular carcinomaHypomethylating prodrugMyelodysplastic syndromeSGI-110ovarian cancer

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Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Decitabine is a well-characterized hypomethylating drug.
  • Hypomethylating agents are crucial in treating hematological malignancies.
  • Existing treatments face challenges with drug clearance and efficacy.

Purpose of the Study:

  • To evaluate SGI-110, a novel hypomethylating prodrug, as a potential cancer therapeutic.
  • To assess the safety, tolerability, and efficacy of SGI-110 in preclinical and clinical settings.
  • To investigate the pharmacokinetic advantages of SGI-110's unique dinucleotide structure.

Main Methods:

  • SGI-110, an oligonucleotide prodrug, was synthesized by linking decitabine to deoxyguanosine.
  • In vitro and animal model systems were used to assess hypomethylation effects.
  • Phase I and II clinical trials were conducted in human patients with various cancers.

Main Results:

  • SGI-110 demonstrated protection from deamination-mediated clearance compared to decitabine.
  • Equivalent or enhanced gene-specific and global hypomethylation effects were observed.
  • The agent proved safe and well-tolerated as a single agent in clinical trials.
  • Promising activity was noted in myelodysplastic syndrome and acute myeloid leukemia patients, including those pretreated with other hypomethylating drugs.

Conclusions:

  • SGI-110 represents a promising second-generation hypomethylating agent with improved stability.
  • Its safety and efficacy profile supports its continued investigation in hematological malignancies and other cancers.
  • SGI-110 offers a potential new therapeutic option for patients with limited treatment alternatives.