Endoxifen is a new potent inhibitor of PKC: a potential therapeutic agent for bipolar disorder.
Protein kinase C (PKC) plays a major role in regulation of both pre and postsynaptic neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. Tamoxifen, a widely used breast cancer drug is known to inhibit PKC and demonstrate antimanic properties in human. We describe herein the synthesis of endoxifen, a tamoxifen active metabolite and compared its PKC inhibitory activity with that of tamoxifen. Endoxifen exhibited fourfold higher potency compared to tamoxifen.
Ali
Shoukath M
SM
Jina Pharmaceuticals, Inc., Libertyville, IL 60048, USA.
Ahmad
Ateeq
A
Shahabuddin
Syed
S
Ahmad
Moghis U
MU
Sheikh
Saifuddin
S
Ahmad
Imran
I
D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D011493:Protein Kinase C