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- W1995584956 abstract "Replacement of the labile sulfhydryl group (-SH) of the hemoregulatory peptide monomer pyroGluGluAspCysLys (HP5b) with an isosteric methylene group yields a chemically stable compound, SK&F108636. In this study, we describe the effects of SK&F108636 on highly enriched Lin−Sca1+ hematopoietic stem cells. SK&F108636 significantly reduced the fraction of cycling progenitor cells, granulocyte macrophage colony-forming cells (GM-CFC), in vitro and in vivo. There was no effect on GM-CFC or Mix-CFC colony formation. SK&F108636 significantly inhibited proliferation of high proliferative potential (HPP)-CFC in semisolid agar cultures stimulated by stem cell factor + interleukin 3 (IL-3) + IL-1, but had no effect in cultures stimulated with M-CSF + IL-3 + IL-1. SK&F108636 was shown to act directly on the stem cells since SK&F108636 inhibited proliferation of Lin−Sca1+ cells in single cell assays. Administration of SK&F108636 to lethally irradiated mice transplanted with 2000 Lin−Sca1+ cells significantly inhibited proliferation/differentiation of cells developing into colony forming units-spleen (CFU-S) (preCFU-S) and the reconstitution of HPP-CFC and GM-CFC. There was no effect of SK&F108636 on CFU-S colony formation or mature cell regeneration in bone marrow, spleen and blood. Hence, the hemoregulatory peptide monomer SK&F108636 is a potent primitive stem cell inhibitor in vivo and in vitro. Inhibition of stem cell proliferation by small specific inhibitors may protect hematopoiesis from myelotoxic side effects during chemotherapy treatment." @default.
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- W1995584956 date "1996-03-01" @default.
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- W1995584956 title "Inhibition of Enriched Stem Cells in Vivo and in Vitro by the Hemoregulatory Peptide SK&F108636" @default.
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- W1995584956 doi "https://doi.org/10.1002/stem.140215" @default.
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