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Niko Klink

@nikolasklink.bsky.social
376 followers 344 following 25 posts

Chemical Biology & drug discovery @Max Planck Dortmund | All things Ubiquitin and bifunctionals @Gersch Lab.

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Niko Klink @nikolasklink.bsky.social · 05/07/2025
Taking these now to our Model Systems (PDAC and melanoma), not only shows highly selective degradation of USP7 by our PROTACs (criteria for matched pair fulfilled!), but also striking differences between inhibitor and degrader treated cells. These differences also occur in many phenotypic assays!
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Niko Klink @nikolasklink.bsky.social · 05/07/2025
After making a bunch of degraders (most not shown here), we arrive at NK250 and NK266 ("Kurt Cubane"), two highly potent USP7 degraders in HiBiT and immune-based assays. NK250, is a faster degrader which we could correlate to its ability to form a stable ternary complex between USP7 and VHL.
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Niko Klink @nikolasklink.bsky.social · 05/07/2025
We introduce NK192, a potent USP7 inhibitor of the widely used hydroxypiperidine scaffold. Converting it through the available exit vector to a biotin probe showed proteome-wide highly selective binding to USP7, fulfilling our criteria for the inhibitor side of the matched chemical pairs.
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Niko Klink @nikolasklink.bsky.social · 05/07/2025
To enable their systematic discovery, we addressed this urgent need with matched chemical pairs of DUB inhibitor and #degraders by focusing on USP7 as a case study. By using potent and selective modulators, we aimed to dissect phenotypes induced by inhibitors and degraders of USP7 in solid cancers.
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