PGP and cancer: Given the excellent brain exposure of 51657, these data would suggest that TPD+ compounds of this type might hold promise for the treatment of brain cancers such as astrocytomas or glioblastomas, as many anti-cancer agents have poor brain penetration due to Pgp efflux at the blood-brain barrier, and there is also evidence of Pgp-mediated drug resistance in some glioblastomas [54].