A new study describes a high affinity interaction between siramesine and phosphatidic acid, a component of cell membranes that also acts as a signalling molecule. Siramesine is a sigma receptor agonist, selective for the σ2 subtype, which was originally under development for the treatment of anxiety but failed to show efficacy in clinical trials.
Siramesine was subsequently shown to kill cancer cells by destabilising their lysosomes. Vincristine, a microtubule destabilising antimitotic drug, which is used in various chemotherapy regimens, greatly sensitised cancer cells to the cytotoxic effects of siramesine.
The new study suggests that it may be possible to design small molecules to specifically scavenge phospholipids involved in the signalling cascades controlling cell survival.