Pharmacological profile of AS1670542, a novel orally-active human thrombopoietin receptor agonist

Eltrombopag an orally-active small molecule thrombopoietin (TPO) receptor agonist was used for the first time in 2008 to treat patients with chronic idiopathic thrombocytopenic purpura Here we investigated the pharmacological effect of a new orally-active small molecule TPO receptor agonist which may be effective in treating these patients 50% effective concentration values for cell proliferation with AS1670542 or eltrombopag were 1 9 and 13 nM respectively while those for megakaryocyte colony formation from human cord blood CD34(+) cells with AS1670542 or eltrombopag were 260 and 950 nM respectively On Day 14 after the start of administration AS1670542 significantly increased the number of human platelets in non obese diabetic/severe combined immunodeficiency (NOD/SOD) mice with transplanted human hematopoietic stem cells at 03 (P<0 05) in contrast while administration of eltrombopag also increased the numbers of these platelets at 30 mg/kg/day (P=0 058) no statistical significance was noted in the Increase Here we identified AS1670542 a novel orally active TPO receptor agonist which mimics the biological activity of TPO and may demonstrate greater in vitro and in vivo pharmacologically efficacy than eltrombopag (C) 2010 Elsevier B V All rights reserved