Granulocyte colony-stimulating factor (G-CSF) stimulates the proliferation of bone marrow granulocytic progenitor cells and promotes their differentiation into granulocytes. G-CSF is therefore an important component of immune defense against pathogenic microorganisms: recombinant human G-CSF (rhG-CSF) is used to treat patients with a variety of neutropenias. In the present study, we screened approximately 10 000 small nonpeptidyl compounds and found 3 small compounds that mimic G-CSF in several in vitro and in vivo assays. These compounds induced G-CSF–dependent proliferation, but had no effect on interleukin-3–dependent, interleukin-2–dependent, interleukin-10–dependent, thrombopoietin (TPO)–dependent, or erythropoietin (EPO)–dependent proliferation. Each compound induced the phosphorylation of signal transducers and activators of transcription–3 (STAT3) and mitogen-activated protein kinase (MAPK) in a G-CSF–dependent cell line and in human neutrophils. In addition, these compounds induced hematopoietic colony formation from primary rat bone marrow cells in vitro. When subcutaneously injected into normal rats, they caused an increase in peripheral blood neutrophil counts. Furthermore, when they were administered to cyclophosphamide-induced neutropenic rats, blood neutrophil levels increased and remained elevated up to day 8. We therefore suggest that these small nonpeptidyl compounds mimic the activity of G-CSF and may be useful in the treatment of neutropenic patients.
Restricting Excessive Cardiac Action Potential and QT Prolongation
Targeting Adhesion Molecules as a Potential Mechanism of Action for Intravenous Immunoglobulin
Altered Dynamics of Action Potential Restitution and Alternans in Humans With Structural Heart Disease
Single-Channel Properties Support a Potential Contribution of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels and If to Cardiac Arrhythmias
QTc Prolongation by Grapefruit Juice and Its Potential Pharmacological Basis
Effect of Adrenergic Stimulation on Action Potential Duration Restitution in Humans
Potential Contribution of NF-B in Neuronal Cell Death in the Glutathione Peroxidase-1 Knockout Mouse in Response to Ischemia-Reperfusion Injury
Potential Consequences for Recruitment, Power, and External Validity of Requirements for Additional Risk Factors for Eligibility in Randomized Controlled Trials in Secondary Prevention of Stroke
Potential Applicability of Recombinant Factor VIIa for Intracerebral Hemorrhage
The National Institute of Biomedical Imaging and Bioengineering: History Status and Potential Impact1