AKR-501

Avatrombopag(AKR-501; AS1670542) is a novel orally-active thrombopoietin(TPO) receptor agonist with EC50 of 3.3 nM.EC50 value: 3.3 nM [1]Target: TPO receptor agonistin vitro: AKR-501 specifically targeted the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as rhTPO did. AKR-501, however, was shown to be effective only in humans and chimpanzees with high species specificity [1]. AS1670542 has 50% effective concentration val
Avatrombopag (Doptelet), is an orally administered, small-molecule thrombopoietin receptor (c-Mpl) agonist which increases platelet number, but not platelet activation,. This decreases the need for blood transfusions. Patients with thrombocytopenia and chronic liver disease (leading to thrombocytopenia) often require platelet transfusions before surgical procedures to decrease the risk of bleeding. Thrombocytopenia (or decreased numbers of platelets) is a common complication in patients suffering from chronic liver disease, either as an immediate result of liver disease or a consequence of interferon-based antiviral therapy. Avatrombopag was approved by the FDA on May 21, 2018 for thrombocytopenia (low platelets) in adults with chronic liver disease who are scheduled to undergo a procedure. It is administered orally as avatrombopag maleate, its salt form. Doptelet (Avatrombopag) is the first orally administered treatment option for patients with chronic liver disease, allowing a large population of patients to avoid a platelet transfusion before a procedure by increasing platelet counts to the optimal level of greater or equal to 50,000 per microliter.|The thrombopoietin receptor agonists mimic the action of thrombopoietin on its receptor and stimulate the activation, proliferation and maturation of megakaryocytes, resulting in an increase in circulating platelet counts. Thrombopoietin itself acts in this manner, but when recombinant thrombopoietins were used clinically, they were found to cause rebound thrombocytopenia, probably due to induction of anti-thrombopoietin antibodies. For this reason, direct administration of thrombopoietin was abandoned as an approach to treating thrombocytopenia and other approaches to activating the thrombopoietin receptor were sought.|Avatrombopag is an orally available platelet thrombopoietin receptor (TPOR; MPL) agonist, with potential megakaryopoiesis stimulating activity. Upon administration, avatrombopag binds to and stimulates TPOR, which may lead to the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. This increases the production of platelets and may prevent chemotherapy-induced thrombocytopenia (CIT). TPOR is a cytokine receptor and member of the hematopoietin receptor superfamily.