MP-Pt(IV)

MP-Pt(IV) is a second-generation, mitochondria-targeted platinum(IV) prodrug designed for the treatment of glioblastoma (GBM). It consists of a methyl-tetrahydropyridine (MP) moiety coupled to a cisplatin precursor. The drug is selectively activated by monoamine oxidase B (MAOB), an enzyme highly expressed in GBM cells. MAOB oxidizes the uncharged MP moiety into a mitochondrially targeted cationic methyl-pyridinium (P+-) form. Once localized in the mitochondria, the Pt(IV) complex is reduced by mitochondrial ascorbate to release active cisplatin, leading to mitochondrial damage and cell death. MP-Pt(IV) has demonstrated efficacy in intracranial patient-derived xenograft mouse models and has been shown to potentiate temozolomide and chemoradiation therapies.