Therapeutic substances that modulate genome methylation

摘要

Compounds containing nucleic acid bases or their precursors modified by enrichment at specific sites with heavy stable isotopes of elements naturally present at those sites in minute amount are useful for the treatment of diseases characterized by altered gene expression and altered pattern of epigenomic control. These compounds, when used as nutrients or in other medicinal application methods, can alter the DNA methylation pattern in a simple way through the well-understood mechanism of kinetic isotope effect (KIE). This effect could also be useful for modifying methylation kinetics in stem cell technology, cloning and as disease therapeutics.

主权项

1. A composition of compounds comprising a compound of the formula: wherein R1 is H, a sugar or substituted sugar moiety, a sugar analogue, or a group which is replaced in vivo by the sugar or substituted sugar moiety or the sugar analogue; wherein R2 is 2H or ZX3 where Z may be 12C or 13C and X may be 2H or 1H; wherein R3 is 1H or 2H; where Q1 and Q2 can be 12C or 13C; and with the provision that at least one atom in R2, R3, Q1 or Q2 is a heavy isotope; wherein the 13C, 2H or both are enriched at least 20% more individually or collectively in comparison to naturally occurring 13C, 2H or both at the same position in the compound, or a pharmaceutically acceptable salt thereof.