Activin Receptor-Like Kinase (ALK) 4/5/7 Inhibitor

Activin receptor-like kinases (ALKs) are members of the type I activin receptor family, and belong to the serine/threonine kinase receptors of the transforming growth factor-β (TGF-β) superfamily.¹⁾ A 83-01 (1) inhibits ALK 4/5/7 and the IC₅₀ values are 45, 12, 7.5 nM, respectively. On the other hand, 1 shows weak inhibition for other ALKs.²⁾ It was reported that 1 could help stabilize rat induced pluripotent stem cells (iPSC) in combination with other chemicals³⁾ and that 1 converts epiblast stem cells (EpiSCs) to an earlier pluripotency state.⁴⁾ It was also reported that the combination of 1 and PD0325901 enables reprogramming of human primary somatic cells to iPSCs with exogenous expression of only OCT4.⁵⁾

References

• 1) Perspectives of small molecule inhibitors of activing receptor‑like kinase in anti‑tumor treatment and stem cell differentiation (Review)
• • X. Cui, S. Shang, X. Lv, J. Zhao, Y. Qi, Z. Liu, Mol. Med. Rep. 2019, 19, 5053.
• 2) The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β
• • M. Tojo, Y. Hamashima, A. Hanyu, T, Kajimoto, M. Saitoh, K. Miyazono, M. Node, T. Imamura, Cancer Sci. 2005, 96, 791.
• 3) Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors
• • W. Li, W. Wei, S. Zhu, J. Zhu, Y. Shi, T. Lin, E. Hao, A. Hayek, H. Deng, S. Ding, Cell Stem Cell 2009, 4, 16.
• 4) Conversion of Mouse Epiblast Stem Cells to an Earlier Pluripotency State by Small Molecules
• • H. Zhou, W. Li, S. Zhu, J. Y. Joo, J. T. Do, W. Xiong, J. B. Kim, K. Zhang, H. R. Schöler, S. Ding, J. Biol. Chem. 2010, 285, 29676.
• 5) Reprogramming of Human Primary Somatic Cells by OCT4 and Chemical Compounds
• • S. Zhu, W. Li, H. Zhou, W. Wei, R. Ambasudhan, T. Lin, J. Kim, K, Zhang, S. Ding, Cell Stem Cell 2010, 7, 651.

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