Therapeutics: Purinergic receptor P2Y G protein-coupled 12 (P2RY12; P2Y12)

Cell culture and mouse studies suggest combining P2RY12 antagonists and tricyclic antidepressants (TCAs) could help treat glioma. In primary mouse gliomal cells and human gliomal cell lines, the P2RY12 antagonist ticlopidine plus the TCA Tofranil imipramine hydrochloride decreased cell viability and increased autophagy compared with either agent alone. In a genetic mouse model of glioma, ticlopidine plus Tofranil decreased tumor size and grade of malignancy and increased tumor cell autophagy and survival. Next steps include testing the combination of TCAs, P2RY12 antagonists and standard of care therapies in preclinical models of glioblastoma.

Mallinckrodt plc markets Tofranil to treat depression and incontinence...