MethylGene Inc. (TSX:MYG) and Pharmion Corporation (NASDAQ:PHRM) today announced a “research collaboration for the development of novel small molecule inhibitors targeting sirtuins, a separate and distinct class of histone deacetylase enzymes (Class 3 HDACs) implicated in cell survival and death.”
MethylGene and Pharmion’s Class I specific HDAC inhibitor, MGCD0103, has demonstrated efficacy in a number of tumor types, and the sirtuins represent potentially attractive novel cancer targets within a related family of enzymes. Sirtuins (including SIRT1) have been shown to deacetylate histone proteins and numerous transcription factors, leading to promotion of normal cell survival and aberrant gene silencing in cancer cells. Inhibition of sirtuins allows reexpression of silenced tumor suppressor genes, leading to reduced growth of cancer cells, and anti-cancer effects have been observed with SIRT1 inhibitors in vitro and in vivo. As yet, no sirtuin inhibitors have entered the clinic. Synergies in gene reexpression have been demonstrated by combining SIRT1 inhibition with either standard cytotoxics or other epigenetic modifying drugs, including inhibitors of DNA methylation and histone deacetylation. Two epigenetic therapy combinations are already under active investigation in Phase II studies combining Pharmion’s Vidaza, a DNA hypomethylating agent, with MethylGene and Pharmion’s HDAC inhibitor, MGCD0103. The parties intend to explore combinations with resulting anti-sirtuins as well.
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