DNA Methyltransferase Inhibitor

　RG 108 (1) is a DNA methyltransferase inhibitor that inhibits the enzyme with IC₅₀ = 115 nM.^1,2) 1 was demonstrated to bind directly to the active site of the enzyme by molecular modeling.¹⁾ Furthermore, 1 enhanced reprogramming of human³⁾ and mouse^4,5) somatic cells to iPS cells.

References

• 1) Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases
• B. Brueckner, R. G. Boy, P. Siedlecki, T. Musch, H. C. Kliem, P. Zielenkiewicz, S. Suhai, M. Wiessler, F. Lyko, Cancer Res. 2005, 65, 6305.
• 2) Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines
• C. Stresemann, B. Brueckner, T. Musch, H. Stopper, F. Lyko, Cancer Res. 2006, 66, 2794.
• 3) Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes
• P. Mali, B.-K. Chou, J. Yen, Z. Ye, J. Zou, S. Dowey, R. A. Brodsky, J. E. Ohm, W. Yu, S. B. Baylin, K. Yusa, A. Bradley, D. J. Meyers, C. Mukherjee, P. A. Cole, L. Cheng, Stem Cells 2010, 28, 713.
• 4) Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule to generate cardiac progenitor cells
• Z. Pasha, H. K. Haider, M. Ashraf, PLoS One 2011, 6, e23667.
• 5) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds
• Y. Shi, C. Desponts, J. T. Do, H. S. Hahm, H. R. Schöler, S. Ding, Cell Stem Cell 2008, 3, 568.