Death metal

The newest cell death pathway ferroptosis could be ripe for investment

The findings in two high profile papers on ferroptosis could be the nudge the fledgling field needs to gain the attention of drug developers. The process is the latest cell death pathway to offer up new targets, with roles in a range of indications, most notably neurodegeneration and cancer.

Unlike the better known pathways apoptosis and necroptosis, ferroptosis depends on iron and involves no caspases. In particular, it has its own genetic and morphological trademark and biology driven by redox chemistry.

Since the pathway was discovered in 2012 by Brent Stockwell’s lab at Columbia University, a spate of ferroptosis studies have defined the major steps linking it to an array of diseases. Stockwell is a professor at Columbia University and co-founder of Kyras Therapeutics Inc. and CombinatoRx Inc.

Blocking the pathway can protect cells in models of neurodegenerative disorders and ischemia-reperfusion. Activating it can kill cancer cells.

Moreover, academic scientists have uncovered at least 20 genes and about 20 compounds that modulate ferroptosis, and several of the compounds could serve as scaffolds for medicinal chemistry (see “Turn-offs & Turn-ons”).


Figure: Turn-ons & turn-offs

The newly described process of ferroptosis - an iron-regulated cell death pathway

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