Explanipedia

Inhibitors supercharge kinase turnover through native proteolytic circuits Open

Katharina Kladnik, Xuefei Guo, Matthias Hinterndorfer, Hlib Razumkov, Polina Prokofeva , et al. · 2025

Targeted protein degradation is a pharmacological strategy that relies on small molecules such as proteolysis-targeting chimeras (PROTACs) or molecular glues, which induce proximity between a target protein and an E3 ubiquitin ligase to pr…

Serendipitous and Systematic Chemoproteomic Discovery of MBLAC2, HINT1, and NME1-4 Inhibitors from Histone Deacetylase-Targeting Pharmacophores Open

Severin Lechner, Shuyao Sha, Jigar P. Sethiya, Patrycja Szczupak, Rafał Dolot , et al. · 2025

Metalloenzyme inhibitors often incorporate a hydroxamic acid moiety to bind the bivalent metal ion cofactor within the enzyme's active site. Recently, inhibitors of Zn²⁺-dependent histone deacetylases (HDACs), including clinical…

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets Open

Martin P. Schwalm, Johannes Dopfer, Adarsh Kumar, Francesco Greco, Nicolas Bauer , et al. · 2024

Decrypting lysine deacetylase inhibitor action and protein modifications by dose-resolved proteomics Open

Yun-Chien Chang, Christian Gnann, Raphael R. Steimbach, Florian Bayer, Severin Lechner , et al. · 2024

Lysine deacetylase inhibitors (KDACis) are approved drugs for cutaneous T cell lymphoma (CTCL), peripheral T cell lymphoma (PTCL), and multiple myeloma, but many aspects of their cellular mechanism of action (MoA) and substantial toxicity …

Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics Open

Stephan Eckert, Nicola Berner, Karl Kramer, Annika Schneider, Julian Müller , et al. · 2024

Proteomics is making important contributions to drug discovery, from target deconvolution to mechanism of action (MoA) elucidation and the identification of biomarkers of drug response. Here we introduce decryptE, a proteome-wide approach …

A region‐resolved proteomic map of the human brain enabled by high‐throughput proteomics Open

Johanna Tüshaus, Amirhossein Sakhteman, Severin Lechner, Matthew The, Eike Mucha , et al. · 2023

Substantial efforts are underway to deepen our understanding of human brain morphology, structure, and function using high‐resolution imaging as well as high‐content molecular profiling technologies. The current work adds to these approach…

Targeting LC3/GABARAP for degrader development and autophagy modulation Open

Martin P. Schwalm, Johannes Dopfer, Adarsh Kumar, Francesco Greco, Nicolas Bauer , et al. · 2023

Recent successes in developing small-molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autopha…

High-Throughput Screening and Proteomic Characterization of Compounds Targeting Myeloid-Derived Suppressor Cells Open

Johannes Krumm, Elissaveta Petrova, Severin Lechner, Julia Mergner, Hans-Henning Boehm , et al. · 2023

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population of incompletely differentiated immune cells. They are known to suppress T cell activity and are implicated in multiple chronic diseases, which make them an attract…

Chemoproteomic target deconvolution reveals Histone Deacetylases as targets of (R)-lipoic acid Open

Severin Lechner, Raphael R. Steimbach, Longlong Wang, Marshall L. Deline, Yun-Chien Chang , et al. · 2023

A region-resolved proteomic map of the human brain enabled by high-throughput proteomics Open

Johanna Tüshaus, Amirhossein Sakhteman, Severin Lechner, Matthew The, Eike Mucha , et al. · 2023

Substantial efforts are underway that aim to deepen our understanding of human brain morphology, structure and function using high-resolution imaging as well has high-content molecular profiling technologies. The current work adds to these…

Decrypting drug actions and protein modifications by dose- and time-resolved proteomics Open

Jana Zecha, Florian Bayer, Svenja Wiechmann, Julia Rechenberger, Nicola Berner , et al. · 2023

Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. In thi…

Chemoproteomic target deconvolution of lipoic acid reveals Histone Deacetylases as the main targets Open

Bernhard Küster, Severin Lechner, Raphael R. Steimbach, Longlong Wang, Patrick Matthias , et al. · 2022

Lipoic acid is an essential enzyme cofactor in central metabolic pathways. Due to its claimed antioxidant properties, racemic (R/S)-lipoic acid is used as a food supplement, but is also investigated as a pharmaceutical in over 180 clinical…

Aza-SAHA Derivatives Are Selective Histone Deacetylase 10 Chemical Probes That Inhibit Polyamine Deacetylation and Phenocopy HDAC10 Knockout Open

Raphael R. Steimbach, Corey J. Herbst‐Gervasoni, Severin Lechner, Tracy Murray Stewart, Glynis Klinke , et al. · 2022

We report the first well-characterized selective chemical probe for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it…

Author Correction: Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target Open

Severin Lechner, Martin Ian P. Malgapo, Christian Grätz, Raphael R. Steimbach, Agnes Baron , et al. · 2022

Development of hetero-triaryls as a new chemotype for subtype-selective and potent Sirt5 inhibition Open

Carina Glas, Eli Naydenova, Severin Lechner, Nathalie Wössner, Yang Liu , et al. · 2022

Aza-SAHA Derivatives are Selective Histone Deacetylase 10 Chemical Probes That Inhibit Polyamine Deacetylation and Phenocopy HDAC10 Knockout Open

Raphael R. Steimbach, Corey J. Herbst‐Gervasoni, Severin Lechner, Tracy Murray Stewart, Glynis Klinke , et al. · 2022

We report the first well-characterized selective chemical probe for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it…

Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target Open

Severin Lechner, Martin Ian P. Malgapo, Christian Grätz, Raphael R. Steimbach, Agnes Baron , et al. · 2022

Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target Open

Severin Lechner, Guillaume Médard · 2022

This dataset contains the untargeted lipidomics data for the publication Lechner et al. 2022 "Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target". The dataset has also been submitted to MetaboLight repo…

Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target Open

Severin Lechner, Guillaume Médard · 2022

This dataset contains the untargeted lipidomics data for the publication Lechner et al. 2022 "Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target". The dataset has also been submitted to MetaboLight repo…

Target deconvolution of HDAC pharmacopoeia highlights MBLAC2 as common off-target Open

Severin Lechner, Martin Ian P. Malgapo, Christian Grätz, Agnès Baron, Patrick Rüther , et al. · 2021

HDAC drugs have entered the pharmacopoeia in the 2000s. However, some enigmatic phenotypes suggest off-target engagement. Here, we developed a chemical proteomics assay using three promiscuous chemotypes and quantitative mass spectrometry …

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