Using Coordination Chemistry to Get Out of ‘Flat Land’


Thu, 30 Mar 2023, 17:00 CEST (Berlin)

Prof. Dr. Seth Cohen, U.C. San Diego, USA

Using Coordination Chemistry to Get Out of ‘Flat Land’

The use of metal complexes to augment or modify existing organic drug-like molecules has been studied for decades. Among the more contemporary and successful efforts in this space has been the use of kinetically and thermodynamically inert metal centers to modify staurosporine, a known kinase inhibitor. These bioinorganic derivatives of staurosporine successfully produced a wide range of selective and potent kinase inhibitors by exploiting the rich 3-dimensional (3D) shapes afforded by these metal centers and their spectator ligands. In these derivatives, the metal centers effectively act as isosteres (or bioisosteres) for a cyclic carbohydrate found in native staurosporine. Inspired by this work and others’, this presentation will focus on the use of small, stable coordination compounds to act as core 3D scaffolds for fragment-based drug discovery (FBDD). Rather than modifying known bioactive molecules, coordination compounds are used as the basis for inhibitor discovery. FBDD may suffer from a lack of 3D organic fragments that coordination compounds can readily provide. The Cohen Lab’s successes and challenges in implementing this strategy, with a focus on coordinate covalent inhibitors of proteases (e.g., the SARS-CoV-2 main protease), will be discussed.

Join in for this exciting BioSolveIT webinar to listen to Seth explaining the details.

Current news

Behind the Scenes of Enamine's REAL Space
April 15, 2024 16:43 CEST
Since its launch in 2018, Enamine’s REAL Space has made a significant impact in revolutionizing the landscape of compound collections. The initial version contained approximately 650 million compounds, establishing itself as one of the expansive catalogs of commercially available molecules for drug discovery. Notably, the first release rivaled even the...
Read on
Martin Schwalm Emerges as Winner of Scientific Challenge Spring 2023
March 15, 2024 14:44 CET
The Scientific Challenge Spring 2023 comes to a conclusion: Martin Schwalm from the University of Frankfurt wins with his project “Identifying Binders to Hijack the Autophagy System for Targeted Protein Degradation”! The study aimed to identify binders for the LC3A protein’s hydrophobic binding site, a crucial target for drug discovery...
Read on
Chemical Space Nagivation CLI Tool Updates
March 12, 2024 15:14 CET
Alongside infiniSee 6 ‘Echo’ we release updates to our command line tools that explore and create Chemical Spaces. Computational and tech-savvy medicinal chemists receive several powerful augmentations to the software; these help fine-tuning search parameters to perform even more efficient screening campaigns. New to those features are the new SMARTS...
Read on