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A Small, Nonpeptidyl Mimic of Granulocyte-Colony- Stimulating Factor

Science  10 Jul 1998:
Vol. 281, Issue 5374, pp. 257-259
DOI: 10.1126/science.281.5374.257

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Abstract

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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: plamb{at}ligand.com

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