#covalentinhibitors — Public Fediverse posts

GTPases have long been considered key examples of undruggable proteins. While this has been overcome for K-Ras using #CovalentInhibitors, for many other family member #DrugDevelopment has not been shown.

Congratulations to Johannes Morstein on winning one of the @GDCh_BioChem Young Scientist Awards for his work addressing this challenge by identifying druggable, allosteric pockets in several GTPases.

https://www.cell.com/cell/fulltext/S0092-8674(24)00908-5
#Biochemistry #ChemBio #GTP #GTPases #Chemistry
CC: @gdch

Great talk by Akane Kawamura at #Biochemistry2026. She talked about her group's exciting work on the #Biochemistry of JmjC demethylases with important implications for #epigenetics. Exciting insights into arginine demethylation.

https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14586

She also talked about the potential of these enzymes in #DrugDiscovery including the discovery of #CovalentInhibitors for KDM5.

https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201810179
#Chemistry #ChemBio #Biochemistry
CC: @gdch, @GDCh_BioChem

I was very happy to be able to talk about some of our work at #Biochemistry2026. I presented results of Patrick Zanon, Marnix Roseboom, Julia Pols and Storm van der Voort on new covalently reactive groups, chemical proteomics methods and screening technologies.

https://www.nature.com/articles/s41557-025-01902-z
#Chemistry #ChemBio #Biochemistry #Chemoproteomics #CovalentInhibitors

Overall, I hope that 2026 will yield at least the same degree of scientific progress as 2025. (12/12)

#Chemistry #ChemBio #Science #Antibiotics #Synthesis #TPD #Degrader #Proteomics #Kinases #RNA #Screening #CovalentInhibitors #DirectToBiology

A covalent KEAP1 activator in the clinics: A team at Vividion led by Matt Patricelli developed a covalent molecular glue for KEAP1, which leads to suppression of NRF2-dependent cancer growth. Excited to see, how the three clinical programs that Vividion built based on #CovalentInhibitors discovered by #ChemicalProteomics will progress. (7/12)
https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-25-1187/771133/A-covalent-allosteric-molecular-glue-suppresses?searchresult=1

Let's start the year off right with an exciting paper post!

In this Chemical Communications paper, the groups of Megan Wright and Stuart Warriner investigate the metal-independent labeling of proteins using isocyanides.

https://pubs.rsc.org/en/content/articlelanding/2026/cc/d5cc04136h
#ChemBio #Chemistry #CovalentInhibitors

Interesting J. Med. Chem. paper by the group of Michael Waring. They developed alkynylpyridopyrimidinones that covalently target Cys775 of EGFR to allow development of #CovalentInhibitors even against the C797S resistance mutant.
https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c02924
#Chemistry #ChemBio #DrugDiscovery #Kinases

Amazing paper by the groups of Li Ye and Ben Cravatt of @scripps.edu in @cp-cell.bsky.social. They developed the vCATCH method to map in vivo, to which tissues and cell types #CovalentInhibitors bind with spatial resolution in whole intact mouse bodies. https://www.cell.com/cell/fulltext/S0092-8674(25)01365-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425013650%3Fshowall%3Dtrue
#Chemistry #ChemBio

Very excited to see this study by the group of David Konrad out in JACS Au.

Ortho-dichloroacrylophenone is a highly reactive, cysteine-directed electrophile for peptide and protein labeling as well as chemoproteomic profiling. Glad that our group could make a small contribution.

https://pubs.acs.org/doi/10.1021/jacsau.5c00692
#ChemBio #Chemistry #ChemPro #ProteoProbes #CovalentInhibitors

Interesting paper by the group of Alexander Dömling in Green Chemistry. They used an Ugi four-component reaction followed by product precipitation for the efficient synthesis and purification of a >1200-member acrylamide library.

https://pubs.rsc.org/en/content/articlelanding/2025/gc/d5gc04440e
#CovalentInhibitors #Chemistry #ChemBio

"Rapid Antibiotic Discovery using a Direct-to-Biology Approach"

Storm van der Voort from the group of Hermen Overkleeft and our group at the @LED3hub presented his exciting research into efficiently finding new antibacterially active #CovalentInhibitors using a direct-to-biology approach and into finding their targets using residue-specific chemoproteomics with the isoDTB-ABPP technology at #NWOCHAINS.

#Bacteria #Antibiotics #Chemistry #ChemBio #ChemicalProteomics #D2B

Insightful talk by Dieuwertje Streefkerk at #NWOCHAINS. She talked about their synthetic work on stereochemically defined sulfur(VI) electrophiles and their use as #CovalentInhibitors on the example of chymotrypsin inhibition.

https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202415873
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201915519
#Chemistry #ChemBio #Electrophiles

Exciting talk by Kevin Neumann at #NWOCHAINS. He talked about the tetrazine- and triazine-thiol exchange reactions for #bioconjugation and #peptide cyclization. He also discussed their potential application for #CovalentInhibitors.

https://onlinelibrary.wiley.com/doi/full/10.1002/psc.3548
https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ceur.202500273
#Chemistry #ChemBio #DrugDiscovery

Great talk by Marta Artola at #NWOCHAINS. She talked about the use of modified sugars as inhibitors and molecular #chaperones in #DrugDiscovery. Exciting insights into the use of cyclic sulfamates and sulfamidates as reactive groups for #CovalentInhibitors.
https://pubs.acs.org/doi/10.1021/acscentsci.7b00214
#Chemistry #ChemBio

We explored the question, from which different areas of chemistry, including glycochemistry, peptide chemistry, materials chemistry and synthetic method development new electrophiles for covalent inhibitors can originate in order to keep expanding the druggable space. (2/2)

#Chemistry #ChemBio #ChemicalProteomics #ChemPro #ProteoProbes #DrugDiscovery #Glycotime #Peptides #Materials #Synthesis #Undruggable #CovalentInhibitors

Now I am looking forward to two days of exciting science, including our focus session on #CovalentInhibitors as well as many exciting presentations by #PhD and #postdoc researchers. (8/8)

Are you interested in novel covalent inhibitors and diverse strategies, through which you can find new chemistries for them? Then check out our Focus Session on "Covalent Inhibitors and where to find them" at the CHAINS conference by NWO. (1/4) #Chemistry #CovalentInhibitors #ChemBio #DrugDiscovery

Are you interested in novel covalent inhibitors and diverse strategies, through which you can find new chemistries for them?

I am very excited that Madeline Kavanagh, Marc Baggelaar, Rita Petracca and I were awarded a Focus Session on "Covalent Inhibitors and where to find them" at the CHAINS conference by NWO to discuss exactly these topics. (1/3)

https://nwochains.nl/programme/novel-covalent-inhibitors-and-where-to-find-them

#Chemistry #CovalentInhibitors #ChemBio #DrugDiscovery

Great opportunity to do a #postdoc in the field of #CovalentInhibitors with a great mentor in the group of Lyn Jones at the Dana Farber Cancer Institute!

https://www.linkedin.com/posts/lynhowardjones_postdoctoral-research-fellow-jones-lab-activity-7354251467450449924-i-CQ?utm_source=share&utm_medium=member_desktop&rcm=ACoAACVzmDsB7J_8sWXEOBYlnnAs1T4cVcDlrxQ

#ChemBio #Chemistry #DrugDiscovery

The final #FlashTalk session gave another exciting overview of different early #DrugDiscovery topics including #CovalentInhibitors for glycosidases (Rob Lammers), host-directed therapies for bacterial infections (Bart van Lieshout) and covalently drugging transcription factors (Shaima Abdalla).

He started by giving a very clear overview of the concept of #CovalentInhibitors and the important advantages that they can have in #DrugDiscovery. He especially highlighted, how powerful covalent fragments can be in this context. (2/7) https://www.sciencedirect.com/science/article/pii/S0165614723001840?via%3Dihub