A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor

Shin Shay Tian, Peter Lamb, Andrew G. King, Stephen G. Miller, Linda Kessler, Juan I. Luengo, Laurie Averill, Randall K. Johnson, John G. Gleason, Louis M. Pelus, Susan B. Dillon, Jonathan Rosen

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152 Scopus citations


A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.

Original languageEnglish (US)
Pages (from-to)257-259
Number of pages3
Issue number5374
StatePublished - Jul 10 1998

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    Tian, S. S., Lamb, P., King, A. G., Miller, S. G., Kessler, L., Luengo, J. I., Averill, L., Johnson, R. K., Gleason, J. G., Pelus, L. M., Dillon, S. B., & Rosen, J. (1998). A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor. Science, 281(5374), 257-259. https://doi.org/10.1126/science.281.5374.257