Thrombopoietin (TPO) is the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.TPO binds to the thrombopoietin receptor (TPOr, also termed c-mpl) on platelets, megakaryocytes, and pluripotent stem cells leading to inhibition of apoptosis of stem cells and megakaryocytes; increased megakaryocyte number, size, and ploidy; increased rate of megakaryocyte maturation and platelet count; and decreased platelet threshold for activation by ADP and collagen.
||Eltrombopag(SB-497115) is a new, orally active thrombopoietin-receptor (c-mpl) agonist that stimulates thrombopoiesis.
||Lusutrombopag is an orally bioavailable thrombopoietin (TPO) receptor agonist, used for treatment of chronic liver disease.