Title:Protein and Small-Molecule Leucopoiesis and Thrombopoiesis Stimulators
Volume: 21
Issue: 13
Author(s): Oldřich Farsa*Peter Zubáč
Affiliation:
- Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Brno,Czech Republic
Keywords:
Colony-stimulating factors, stem-cell factors, pegylation, plerixafor, thrombopoietin, romiplostim, eltrombopag.
Abstract: Pluripotent stem cells of the bone marrow are stimulated by different cytokines to proliferation
and differentiation into various types of blood cells. These cytokines are mostly glycoproteins.
Erythropoietin stimulates stem cells to the formation of erythrocytes while colony-stimulating factors
cause the formation of different types of white blood cells. Stem cell factors play an important role in
the maintenance and survival of blood cells of all types. Thrombopoietin stimulates stem cells to proliferation
and formation of blood platelets. Granulocyte colony-stimulating factor is probably the most
important drug in use. It stimulates stem cells to the formation of neutrophile granulocytes. It is often
used in recombinant forms such as filgrastim in the treatment of neutropenia in cancer chemotherapy
or AIDS. Its pegylated conjugates such as pegfilgrastim are also available. Its activity can be supported
by plerixafor, a small molecule – bicyclam derivative acting as an indirect agonist of stem cells
factor. It acts as an antagonist of CXCR4 receptor activation of which brakes hematopoiesis. The
treatment of conditions accompanied by thrombocytopenia such as idiopathic thrombocytopenic purpura
is currently not performed by thrombopoietin but synthetic agonists of its receptor are preferred.
Romiplostim is a peptibody. It consists of a protein part interacting with the thrombopoietin receptor
which is, however, different from thrombopoietin, and of Fc fragment of immunoglobulin G1. In contrast,
small molecule thrombopoietin receptor agonists represented by eltrombopag can be given orally
unlike all of the above.
