Membrane permeable lipophilic cations as mitochondrial directing groups
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Updated: Apr 16, 2026

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
Published on: February 25, 2016
Joseph T Madak, Nouri Neamati1
1Department of Medicinal Chemistry, College of Pharmacy, Translational Oncology Program, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Bldg 520, Ann Arbor, MI 48109, USA. neamati@umich.edu.
Abstract:
The mitochondrion's negatively charged membrane potential has been well documented to drive the accumulation of membrane permeable delocalized lipophilic cations (DLC). DLC attachments to known bioactive compounds can direct organelle localization and improve drug exposure to targets within the mitochondria. Due to the mitochondria's essential function and its regulation of cell death, DLC targeted therapies are the focus of drug discovery projects altering cellular fate via mitochondrial targets. This review provides an update on recent developments for the two main applications of DLCs: cytoprotective therapies aimed at reducing oxidative stress and cytotoxic therapies aimed at initiating cell death for the treatment of various cancers. Both approaches have produced significant improvements using DLC conjugated compounds that include improved potency, pharmacokinetic properties, and the potential to overcome resistance mechanisms.
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