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Updated: Jun 12, 2026

Characterizing Mammalian Zinc Transporters Using an In Vitro Zinc Transport Assay
Published on: June 2, 2023
Zinc is not required for activity of TPO agonists acting at the c-Mpl receptor transmembrane domain
Abstract:
Molecules that mimic the cytokine thrombopoietin that act by an atypical mechanism of binding to a receptor transmembrane (TM) domain are widely understood to require zinc for their biological activity. We investigated potent thrombopoietin mimetics from three chemical classes including the recently registered drug Eltrombopag, which operate via this novel mechanism, to determine whether zinc is essential for inducing cell proliferation. Using addition of zinc and a potent metal chelator, we show that the existing paradigm is incorrect and the compounds exhibit excellent thrombopoietin-mimetic activity even in the presence of high concentrations of EDTA. The implications of these findings for the mechanism of action are discussed.
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