Intracellular lipid binding proteins as gatekeepers of drug activity

Many contemporary drug targets are associated with signalling pathways and receptors in the cytosol and intracellular organelles. Cellular transport to these targets is therefore a critical requirement for drug activity and yet the aqueous solubility of many drug molecules is insufficient to support passive diffusion across the cytosol. Here we explore the hypothesis that endogenous lipid transport pathways serve as gatekeepers of drug activity by dictating access to intracellular targets. This holds the potential for the design of improved drug candidates with structural signatures that bind not only to the target, but which also facilitate interaction with the cellular machinery required to facilitate cellular delivery.