Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis
K Thompson, MJ Rogers, FP Coxon… - Molecular pharmacology, 2006 - Elsevier
Bisphosphonates such as alendronate and zoledronate are blockbuster drugs used to
inhibit osteoclast-mediated bone resorption. Although the molecular mechanisms by which
bisphosphonates affect osteoclasts are now evident, the exact route by which they are
internalized by cells is not known. To clarify this, we synthesized a novel, fluorescently
labeled analog of alendronate (AF-ALN). AF-ALN was rapidly internalized into intracellular
vesicles in J774 macrophages and rabbit osteoclasts; uptake of AF-ALN or [14 C] …
inhibit osteoclast-mediated bone resorption. Although the molecular mechanisms by which
bisphosphonates affect osteoclasts are now evident, the exact route by which they are
internalized by cells is not known. To clarify this, we synthesized a novel, fluorescently
labeled analog of alendronate (AF-ALN). AF-ALN was rapidly internalized into intracellular
vesicles in J774 macrophages and rabbit osteoclasts; uptake of AF-ALN or [14 C] …