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Printed Magazine "TCIMAIL" > TCIMAIL Back Numbers 2014 >

MEK Inhibitor

No.163(October 2014)

A2529: 2-(2-Amino-3-methoxyphenyl)chromone (1)

The homeodomain protein Nanog plays an essential role in the self-renewal of embryonic stem (ES) cells.^1-3) On the other hand, it was reported that Nanog gene repression was primarily mediated by the Grb2/Mek pathway.⁴⁾ 2-(2-Amino-3-methoxyphenyl)chromone (PD 98059, 1) is a MAPK/ERK kinase (MEK) inhibitor^5,6) and used as one of the biologically active small molecules in the study described above.⁴⁾

Grb2: growth factor receptor-bound protein 2
MAPK: mitogen-activated protein kinase
ERK: extracellular signal-regulated kinase

References

1)The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells
- K. Mitsui, Y. Tokuzawa, H. Itoh, K. Segawa, M. Murakami, K. Takahashi, M. Maruyama, M. Maeda, S. Yamanaka, Cell 2003, 113, 631.
2)Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells
- I. Chambers, D. Colby, M. Robertson, J. Nichols, S. Lee, S. Tweedie, A. Smith, Cell 2003, 113, 643.
3)Nanog is the gateway to the pluripotent ground state
- J. Silva, J. Nichols, T. W. Theunissen, G. Guo, A. L. van Oosten, O. Barrandon, J. Wray, S. Yamanaka, I. Chambers, A. Smith, Cell 2009, 138, 722.
4)The Grb2/Mek pathway represses Nanog in murine embryonic stem cells
- T. Hamazaki, S. M. Kehoe, T. Nakano, N. Terada, Mol. Cell. Biol. 2006, 26, 7539.
5)A synthetic inhibitor of the mitogen-activated protein kinase cascade
- D. T. Dudley, L. Pang, S. J. Decker, A. J. Bridges, A. R. Saltiel, Proc. Natl. Acad. Sci. USA 1995, 92, 7686.
6)PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo
- D. R. Alessi, A. Cuenda, P. Cohen, D. T. Dudley, A. R. Saltiel, J. Biol. Chem. 1995, 270, 27489.

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