Knapp

Stefan Knapp

Affiliations

Goethe University

Biography

Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He remains associated to the SGC as a visiting Professor at Oxford and he is also adjunct Professor of the George Washington University. Since 2017 he is the CSO of the newly founded SGC node at the Goethe-University Frankfurt. His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules that function as reader domains of the epigenetic code.

Research Areas

My laboratory is interested in understanding molecular mechanisms that regulate protein function of key signalling molecules and how these mechanisms can be utilized for the development of highly selective and potent inhibitors (chemical probes). As a basis for this work we have generated a comprehensive set of high resolution crystal structures that cover most members of the protein family of interest. We are particularly interested in protein interactions module of the bromodomain family that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. This effort generated several highly selective chemical probes targeting bromodomains. A second research focus is on protein kinases. Our laboratory has solved a comprehensive set of crystal structure of this large protein family offering the opportunity to understand molecular mechanisms of their regulation and developing new strategies for their selective targeting. We developed for example a number of highly selective inhibitors by exploring unusual binding modes and allosteric binding sites. A particular focus of the laboratory is also to understand structural mechanisms leading to slow binding kinetics as part of the K4DD consortium.

All Publications

2023

Mutation in the Common Docking Domain Affects MAP Kinase ERK2 Catalysis and Stability.

Novak L, Petrosino M, Pasquo A, Chaikuad A, Chiaraluce R, Knapp S, Consalvi V

Cancers (Basel). 2023-5-26 . 15(11): .doi: 10.3390/cancers15112938

PMID: 37296900

Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1Îµ vs Casein Kinase 1Î´.

Choi JY, Noguchi Y, Alburger JM, Bayle S, Chung E, Grant W, Chaikuad A, Knapp S, Duckett DR, Roush WR

J Med Chem. 2023-5-19 . .doi: 10.1021/acs.jmedchem.2c01180

PMID: 37204207

Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily.

Rak M, Tesch R, Berger LM, Shevchenko E, Raab M, Tjaden A, Zhubi R, Balourdas DI, Joerger AC, Poso A, KrÃ¤mer A, Elson L, LuÄiÄ‡ A, Kronenberger T, Hanke T, Strebhardt K, Sanhaji M, Knapp S

Eur J Med Chem. 2023-4-7 . 254:115347 .doi: 10.1016/j.ejmech.2023.115347

PMID: 37094449

Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum.

Tredup C, Ndreshkjana B, Schneider NS, Tjaden A, Kemas AM, Youhanna S, Lauschke VM, Berger BT, Krämer A, Berger LM, Röhm S, Knapp S, Farin HF, Müller S

ACS Chem Biol. 2023-3-21 . .doi: 10.1021/acschembio.2c00877

PMID: 36944371

Chemistry-led investigations into the mode of action of NAMPT activators, resulting in the discovery of non-pyridyl class NAMPT activators.

Tang S, Garzon Sanz M, Smith O, Krämer A, Egbase D, Caton PW, Knapp S, Butterworth S

Acta Pharm Sin B. 2023-3-7 . 13(2):709-721 .doi: 10.1016/j.apsb.2022.07.016

PMID: 36873168

Oxazolo[5,4-f]quinoxaline-type selective inhibitors of glycogen synthase kinase-3α (GSK-3α): Development and impact on temozolomide treatment of glioblastoma cells.

Hasyeoui M, Lassagne F, Erb W, Nael M, Elokely KM, Chaikuad A, Knapp S, Jorda A, Vallés SL, Quissac E, Verreault M, Robert T, Bach S, Samarat A, Mongin F

Bioorg Chem. 2023-3-4 . 134:106456 .doi: 10.1016/j.bioorg.2023.106456

PMID: 36913879