Protein Arginine Methyltransferase Inhibitor

Since Yamanaka et al. identified transcription factors for inducing pluripotent stem cells from somatic cells, Oct4, Klf4, Sox2, and cMyc, technologies to establish induced pluripotent stem (iPS) cells have been developed.¹⁾ It was reported that reprogramming neural progenitor cells and fibroblasts is possible through combination with small molecules: two or three transcription factors and even one factor, Oct4. Several related articles are shown in the Table.^2,3)
　AMI-5 (1) is a small molecule known not only as a color pigment but also as a protein arginine methyltransferase (PRMT1) inhibitor (Table 1).⁴⁾ Yuan et al. reported that 1 enables Oct4-induced reprogramming of mouse embryonic fibroblasts in combination with TGF-β inhibitor, A 83-01.⁵⁾

* 1 is widely known as Tetrabromofluorescein or Eosin Y.

References

• 1) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
• K. Takahashi, S. Yamanaka, Cell 2006, 126, 663.
• 2) Reprogram or reboot: Small molecule approaches for the production of induced pluripotent stem cells and direct cell reprogramming
• D.-W. Jung, W.-H. Kim, D. R. Williams, ACS Chem. Biol. 2014, 9, 80.
• 3) Small molecules and small molecule drugs in regenerative medicine
• B. Lu, A. Atala, Drug Discov. Today 2014, 19, 801.
• 4) Small molecule regulators of protein arginine methyltransferases
• D. Cheng, N. Yadav, R. W. King, M. S. Swanson, E. J. Weinstein, M. T. Bedford, J. Biol. Chem. 2004, 279, 23892.
• 5) Brief report: Combined chemical treatment enables Oct4-induced reprogramming from mouse embryonic fibroblasts
• X. Yuan, H. Wan, X. Zhao, S. Zhu, Q. Zhou, S. Ding, Stem Cell 2011, 29, 549.

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