Mario van der Stelt

Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474 A drug that was unexpectedly neurotoxic in a clinical trial has off-target activities in chemical proteomic assays.

It also highlights work by the group of @mvdstelt.bsky.social of the @led3hub.bsky.social on profiling the targets of BIA 10-2474 (www.science.org/doi/10.1126/...) as well as the work that @mads-chem.bsky.social performed in Ben Cravatt's lab on JAK1 inhibitors (www.nature.com/articles/s41...) (4/5)

Probing the proteome - Nature Biotechnology Chemical proteomics has brought rigor to covalent drug discovery and drugs to the clinic. Can it deliver a new generation of drug targets?

A new exciting article in @natbiotech.nature.com highlights the power of chemical proteomics to find druggable pockets on difficult high-value targets. Great insights into applications in covalent and non-covalent drug discovery including clinical development. (1/5) www.nature.com/articles/s41...

A great talk by Joel Rüegger of the group of @mvdstelt.bsky.social at #FocusOnCovalentDrugs. He talked about his amazing work in the @led3hub.bsky.social on the CellEKT platform for profiling target engagement of kinase inhibitors in living cells. (1/5) www.mcponline.org/article/S153...

Lipidation of proteins has diverse essential roles in biology.

In his amazing keynote lecture at #Lunteren, Marc Baggelaar talked about his group's exciting contributions to better understand protein lipidations using #ChemicalProteomics. (1/5)
#chemsky #ChemBio

The Continuing Crisis, Part VII: An Overview

Another “Continuing Crisis” post, this one covering some larger principles and explaining why I’m doing these in general:

Congratulations and a big thank you to @verenas.bsky.social and the labs of Istvan Katona, Yulong Li, Nephi Stella, and Laura Heitman, Coen van Hasselt at @led3hub.bsky.social and @unileiden.bsky.social for a fantastic collaboration. 4/4

Mathematical modelling provided a comprehensive understanding of endocannabinoid signaling. The model addresses key questions in the field and suggests that microvesicles carrying signaling lipids in their membrane regulate neuronal functions in parallel to synaptic vesicles. n/3

Our findings led us to propose an “on demand release” model, where microvesicle formation governs endocannabinoid release. This model reconciliates three previously proposed hypotheses for endocannabinoid trafficking. n/2

Happy to announce on my first bsky post that today our manuscript “The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles” has been published in its final form in PNAS n/1