title: Developing drugs targeting transition metal homeostasis.
abstract: Metal dyshomeostasis is involved in the pathogenesis and progression of diseases including cancer and neurodegenerative diseases. Metal chelators and ionophores are well known modulators of transition metal homeostasis, and a number of these molecules are in clinical trials. Metal-binding compounds are not the only drugs capable of targeting transition metal homeostasis. This review presents recent highlights in the development of chelators and ionophores for the treatment of cancer and neurodegenerative disease. Moreover, we discuss the development of small molecules that alter copper and iron homeostasis by inhibiting metal transport proteins. Finally, we consider the emergence of metal regulatory factor 1 as a drug target in diseases where it mediates zinc-induced signalling cascades leading to pathogenesis.
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Weekley
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: chuanhe@uchicago.edu.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000378:metabolism; D028561:Transition Elements / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D007476:Ionophores; D026901:Membrane Transport Proteins; D028561:Transition Elements