Journal article
The ribosome biogenesis inhibitor CX-5461 increases platelet count in humans and enhances murine megakaryopoiesis
Vijay Bhoopalan, Amandeep Kaur, James Hearn, Kylee Maclachlan, Lixinyu Liu, Rita Ferreira, Sidra Ali, Yee-Lin Thong, Nadine Hein, Simone Brysland, Si Ming Man, Simon Harrison, Robert Andrews, Koji Eto, Philip Choi, Jiayu Wen, Ross Hannan, Elizabeth Gardiner
Blood | American Society of Hematology | Published : 2025
Abstract
Abstract Treatment of sub-optimal platelet production and thrombocytopenia remains a major clinical challenge and thrombocytopenia is a common and serious complication of anticancer therapies. Here, we identify a novel thrombopoietic activity of the first-in-class ribosome biogenesis inhibitor CX-5461. In a phase I trial, 56% (9/16) of patients with haematological malignancy (myeloma, lymphoma, or leukaemia) exhibited up to a 34% increase in platelet count following a single dose of CX-5461. C57BL/6 or thrombopoietin (TPO)-receptor-deficient mice received three doses/week of 35 mg/kg CX-5461 or vehicle. CX-5461 elicited a rapid, rev..
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