Progen targets epigenetics
Monday, 20 April, 2009
Despite its recent dramas, Brisbane Progen Pharmaceuticals is currently developing new anti-cancer compounds aimed at demethylating DNA and inhibiting the proliferation of cancer cells, the company says.
In a presentation to the American Association for Cancer Research conference in Colorado over the weekend, researchers from Johns Hopkins University School of Medicine and Progen scientists produced data showing the company’s polyamine analogue PG-11144 effectively inhibited the activity of lysine-specific demethylase 1 (LSD1), an enzyme that catalyses the demethylation of certain histone lysines.
Inhibiting LSD1 resulted in the re-expression of epigenetically silenced tumour suppressor genes in the Wnt signalling pathway, particularly when combined with the DNA methyltransferase inhibitor DAC, the researchers reported.
Company scientists also reported that another polyamine analogue, PG11047, was able to induce the rate-limiting enzymes SSAT and SMO in rapidly dividing cells.
They found that the combination of PG11047 and cis-platin had a potent anti-tumour effect in a pre-clinical model of lung and prostate cancer. The company is currently in Phase 1 clinical trials to determine the most promising indications.
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