BIX01294 (hydrochloride hydrate)

Description

The methylation of lysine residues on histones plays a central role in determining euchromatin structure and gene expression. The histone methyltransferase (HMTase) G9a can mono- or dimethylate lysine 9 on histone 3 (H3), contributing to early embryogenesis, genomic imprinting, and lymphocyte development.^1,2,3 BIX01294 (hydrochloride hydrate) is a selective inhibitor of G9a HMTase (IC₅₀ = 1.7 μM).⁴ It less effectively inhibits the HMTase G9a-like protein (GLP; IC₅₀ = 38 μM) and has no effect on other known HMTases.⁴ BIX01294 has been used in combination with the calcium channel activator BayK8644 to facilitate the generation of induced pluripotent stem cells from somatic cells in vitro.⁵

References

1. Tachibana, M., Sugimoto, K., Nozaki, M., et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis Genes Dev. 16(14),1779-1791(2002).
2. Wagschal, A., Sutherland, H.G., Woodfine, K., et al. G9a histone methyltransferase contributes to imprinting in the mouse placenta Mol. Cell Biol. 28(3),1104-1113(2008).
3. Thomas, L.R., Miyashita, H., Cobb, R.M., et al. Functional analysis of histone methyltransferase G9a in B and T lymphocytes J. Immunol. 181(1),485-493(2008).
4. Kubicek, S., O'Sullivan, R.J., August, E.M., et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase Mol. Cell 25,473-481(2007).
5. Shi, Y., Desponts, C., Do, J.T., et al. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds Cell Stem Cell 3(5),568-574(2008).