PMID: 25732791Mar 4, 2015Paper

Membrane permeable lipophilic cations as mitochondrial directing groups

Current Topics in Medicinal Chemistry
Joseph T Madak, Nouri Neamati

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.

Citations

Aug 27, 2016·ACS Medicinal Chemistry Letters·Tianming YangOi Lian Kon
Dec 28, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Yanxi LiuZhou Zhou
Aug 6, 2019·Chemical Communications : Chem Comm·Yu GengYouqing Shen
Oct 28, 2016·MedChemComm·Calabrese GianpieroTsibouklis John
Apr 7, 2017·Interface Focus·Kylie YangElizabeth J New
Aug 4, 2018·Frontiers in Microbiology·Huan ChenMei L Go
Dec 14, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yanxi LiuZhou Zhou
Aug 24, 2017·Chemistry : a European Journal·Joseph T MadakNouri Neamati
Sep 24, 2020·Biomolecules·Svyatoslav S SokolovFedor F Severin
Jul 28, 2021·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Benjamin W SchlichtmannBalaji Narasimhan
Nov 21, 2017·ACS Medicinal Chemistry Letters·Ming LiMei-Lin Go
Sep 2, 2021·JACC. Basic to Translational Science·Anja KarlstaedtBonnie Ky

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