Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Brno, Czech Republic.
Mini Rev Med Chem. 2021;21(13):1638-1645. doi: 10.2174/1389557521999201230195926.
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.
骨髓中的多能干细胞被不同的细胞因子刺激增殖，并分化为各种类型的血细胞。这些细胞因子大多是糖蛋白。促红细胞生成素刺激干细胞形成红细胞，而集落刺激因子导致不同类型的白细胞形成。干细胞因子在维持和存活各种类型的血细胞中发挥重要作用。血小板生成素刺激干细胞增殖和形成血小板。粒细胞集落刺激因子可能是目前使用的最重要的药物。它刺激干细胞形成中性粒细胞。它经常以重组形式如非格司亭用于癌症化疗或艾滋病引起的中性粒细胞减少症的治疗。其聚乙二醇化缀合物如培非格司亭也可应用。它的活性可以通过plerixafor 来支持，plerixafor 是一种小分子 - 双环酰胺衍生物，作为干细胞因子的间接激动剂。它作为 CXCR4 受体的拮抗剂，其激活会阻止造血。目前，血小板减少症伴随的疾病如特发性血小板减少性紫癜的治疗不是通过促血小板生成素进行的，而是优先选择其受体的合成激动剂。罗米司亭是一种肽结合物。它由与促血小板生成素受体相互作用的蛋白质部分组成，但与促血小板生成素不同，还有免疫球蛋白 G1 的 Fc 片段。相比之下，以 eltrombopag 为代表的小分子促血小板生成素受体激动剂与上述所有药物不同，可口服给予。
