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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
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Developing drugs targeting transition metal homeostasis.

Claire M Weekley1, Chuan He1

  • 1Department 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.

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This review explores novel drug development for cancer and neurodegenerative diseases by targeting metal homeostasis. It highlights chelators, ionophores, and small molecules modulating metal transport and zinc signaling pathways.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Neuroscience

Background:

  • Metal dyshomeostasis is implicated in cancer and neurodegenerative disease pathogenesis.
  • Metal chelators and ionophores are established modulators of transition metal homeostasis, with some in clinical trials.

Purpose of the Study:

  • To review recent advancements in developing chelators and ionophores for treating cancer and neurodegenerative diseases.
  • To discuss novel small molecules targeting metal transport proteins for copper and iron homeostasis.
  • To explore metal regulatory factor 1 as a potential drug target in diseases involving zinc-induced signaling.

Main Methods:

  • Literature review of recent developments in metal-modulating compounds.
  • Analysis of small molecules inhibiting metal transport proteins.
  • Examination of metal regulatory factor 1's role in disease pathogenesis.

Main Results:

  • Highlights recent progress in chelator and ionophore development for cancer and neurodegenerative disease treatment.
  • Discusses emerging small molecules that modulate copper and iron homeostasis by inhibiting transport proteins.
  • Identifies metal regulatory factor 1 as a promising drug target for specific diseases.

Conclusions:

  • Metal-binding compounds offer diverse therapeutic strategies for metal dyshomeostasis-related diseases.
  • Targeting metal transport proteins and zinc signaling pathways presents new avenues for drug development.
  • Further research into metal regulatory factor 1 could yield novel treatments for complex diseases.