A new way to target the ferroptosis regulator GPX4

Today my lab published a paper in Cell Chemical Biology describing a new way of targeting the central regulator of ferroptosis — the lipid repair enzyme glutathione peroxidase 4 (GPX4).

Here is the paper, with free download for the next 50 days:

https://authors.elsevier.com/a/1g8458jWWJpk2b

In short, we found a new site on this protein at cysteine 66 that can be targeted with electrophilic small molecules. We solved numerous high resolution x-ray structures of different compounds bound to this site, revealing how even better compounds can be designed.

Here is what the site looks like:

From the big picture perspective, this is exciting to us because GPX4 is essential in some of the more aggressive and otherwise drug-resistant cancers. Our new paper suggests a strategy for treating these aggressive, drug-resistant cancers. There is still a long way to go to create a drug that acts through this mechanism, of course, but this opens a door to a new strategy. I hope you enjoy reading.

I was happy to see that our paper was highlighted on the cover of the Dec 15th issue of Cell Chemical Biology!

https://www.cell.com/ccbio/issue?pii=S2451945621X0013X#closeFullCover

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