Negatively charged intracellular compartments and membranes

The target referred to as other cellular membranes and negatively charged intracellular compartments is a pharmacological designation for the non-specific sites of action and sequestration for polycationic and amphiphilic drugs. This category encompasses various lipid bilayers and organelles, including the bacterial outer membrane, the inner mitochondrial membrane, and lysosomes, which are characterized by a high density of anionic phospholipids or a significant negative membrane potential. Drugs such as polymyxins and cationic ceramides utilize electrostatic attraction to bind these sites, leading to membrane permeabilization or organelle-specific signaling. While this targeting is essential for the efficacy of certain antibiotics and experimental cancer therapies, interaction with these compartments in human tissues—particularly the renal proximal tubules—is a primary cause of drug-induced nephrotoxicity and phospholipidosis. Consequently, this target represents both a therapeutic opportunity for selective drug delivery and a significant challenge for drug safety and pharmacokinetics. Understanding the molecular basis of these interactions is critical for the development of next-generation therapeutics with improved specificity and reduced off-target effects.

Other names

Anionic membranesAcidic organellesLysosomesMitochondrial membranesBacterial membranesOther cellular membranes and negatively charged intracellular compartments

Electrostatic binding to anionic phospholipids (e.g., Lipid A, Phosphatidylserine, Cardiolipin) and accumulation driven by negative membrane potential.