P-gp is a particularly challenging target because of its intrinsic structural properties (large structure, lack of conventional druggable pockets, etc.) with are related to its biological role. P-gp affects the bioavailability of drugs and is involved in multidrug resistance by transporting xenobiotics from the cell membrane to the extracellular space, thus limiting their absorption and intracellular accumulation. Clinical effective inhibitors are still lacking as most of the currently available drugs failed in reducing multidrug resistance or caused severe side effects.