AACR 2007: SuperGen Showcases Selective Degradation of DNMT1
Apr 19, 2007 cancer
At the 2007 annual meeting of the American Association for Cancer Research (AACR), pharmaceutical company SuperGen (NASDAQ:SUPG) presented data on a class of quinilone-based compounds that are not incorporated into DNA, selectively induce the degradation of DNA Methyltransferase I (DNMT1) in human cancer cells and re-express silenced tumor supressor genes.
Researchers have discovered a novel class of quinoline-based compounds that are not incorporated into DNA and cause selective degradation of DNMT1 in human cancer cells with minimal or no effects on DNMT3A and DNMT3B that have been discovered. This addresses an issue with re-activation of silenced tumor suppressor genes by 5-Azacytidine (5-AzaC or Vidaza) and its congener 5-aza- deoxycydinite (5-aza-CdR or Decitabine or Dacogen). These compounds provide a different mechanistic approach to the creation of cancer therapies because they selectively and rapidly induce degradation of maintenance DNA methyltransferase, DMNT1. However, they show some toxicity due to their incorporation into the cell DNA. One compound in particular, S1027, resulted in complete degradation of DNMT1 within 24 hours of treatments and also blocked degradation as a pre-treatment of cells with proteasomal inhibitors.
SuperGen also showcased their work showing that zebrafish provide an excellent screening model for small molecule inhibitors of DNMT1. Link
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