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Reposted by Martin Schwalm

Zuzanna Kozicka @zkozicka.bsky.social · Mar 18

Very excited for our next seminar this Thursday, March 20th:
Martin Schwalm (@thesgc.bsky.social, formerly Knapp lab) will share insights on UPS inhibitors and Dean Clift (TRIMTECH Tx) will discuss hijacking TRIM21 for protein #degradation!

👉Join us at 12 PM EST/ 5 pm CET (‼️ US/EU time mismatch ‼️)

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Reposted by Martin Schwalm

Keith Hornberger @krhornberger.bsky.social · Jan 21

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation

Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately opti...

pubs.acs.org

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Martin Schwalm @martinschwalm.bsky.social · Jan 17

We got the 3. journal cover. This time depicting the UPS inhibitors interfering with the different steps of the cascade in @acs.org Chemical Biology.
pubs.acs.org/toc/acbcct/c...

Reposted by Martin Schwalm

Joachim Goedhart @joachimgoedhart.bsky.social · Jan 6

A photoswitchable HaloTag for spatiotemporal control of fluorescence in living cells by @clairedeo.bsky.social and team:
www.biorxiv.org/content/10.1...

General principle of photoswitchable HaloTag (psHaloTag) and open-closed equilibrium of JF635-HaloTag ligand (HTL).

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Martin Schwalm @martinschwalm.bsky.social · Jan 6

Interesting review on TPD which still describes ATTECs as LC3 binding molecules. The paper was revised a month after we published our results that there is no binding to LC3...
www.sciencedirect.com/science/arti...

See our paper here:
www.nature.com/articles/s41...

Recent advances in developing targeted protein degraders

Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited …

www.sciencedirect.com

Reposted by Martin Schwalm

Geordi Frere @geordifrere.bsky.social · Jan 4

A rigorous study of UPS tool compounds for #degrader evaluation is published by Stefan Knapp @thesgc.bsky.social in ACS Chemical Biology! They determine the optimal doses of UPS pathway inhibitors that rescue degradation without displaying off-target activity and toxicity.
dx.doi.org/10.1021/acsc...

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation

Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately opti...

dx.doi.org

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Martin Schwalm @martinschwalm.bsky.social · Jan 4

Interested in #TPD? This might be for you. What concentrations of UPS inhibitors are safe to use to prove your proteasome dependent degradation mechanism?

#PROTAC #TPD #degradation #Science #drugdiscovery

pubs.acs.org/doi/10.1021/...

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation

Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately opti...

pubs.acs.org

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Martin Schwalm @martinschwalm.bsky.social · Dec 18

Great to contribute to this study. We report on a target-hopping approach for the discovery of novel MLK3 inhibitors

pubs.acs.org/doi/10.1021/...

#KinaseInhibitors #DrugDiscovery #TargetedTherapies

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important ro...

pubs.acs.org

Martin Schwalm @martinschwalm.bsky.social · Dec 6

Quality control is often overlooked in novel pathways, and we demonstrate this using ATTECs (Autophagy Tethering Compounds) as a case study. Our new study highlights what’s frequently missing in research!
#ProteinDegradation
Just out in @naturecomms.bsky.social
www.nature.com/articles/s41...

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets - Nature Communications

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but e...

www.nature.com

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Reposted by Martin Schwalm

Ingo Hartung @hartungingo.bsky.social · Nov 25

There are no shortcuts in drug discovery. And it takes incredible efforts to make sense of what you can find in the scientific literature. This is an excellent piece of work to quality check what has been claimed as a new avenue in targeted protein degradation (TPD). www.nature.com/articles/s41...

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets - Nature Communications

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but e...

www.nature.com

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Reposted by Martin Schwalm

Derek Lowe @dereklowe.bsky.social · Dec 3

That awkward moment when someone publishes a paper saying that they can’t find any evidence that your compounds bind to what your own series of papers say that they bind to. . .

Do They Even Bind?

www.science.org

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Martin Schwalm @martinschwalm.bsky.social · Dec 6

Thanks Alessio! It's good to see that this seems to be sparking a lot of discussion.

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