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.
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.
Dettenhöfer M, Tandara LN, Amrhein JA, Kurz CG, Schwalm MP, Mensing TE, Wahl LM, Krämer A, Gerninghaus J, Lenz C, Elson L, Berger BT, Schröder M, Saxena K, Müller S, Knapp S, Greco FA, Hanke T
ACS Med Chem Lett. 2025-11-19 . 16(11):2086-2096 .doi: 10.1021/acsmedchemlett.5c00479
PMID: 41256983Hank EC, D'Arcy-Evans ND, Scaletti ER, Benítez-Buelga C, Wallner O, Ortis F, Zhou K, Meng L, Del Prado A, Calvo P, Almlöf I, Wiita E, Nierlin K, Košenina S, Krämer A, Eddershaw A, Kehler M, Long M, Jemth AS, Dawson H, Stewart J, Dickey A, Astorga ME, Varga M, Homan EJ, Scobie M, Knapp S, Sastre L, Stenmark P, de Vega M, Helleday T, Michel M
RSC Chem Biol. 2025-11-6 . .doi: 10.1039/d4cb00323c
PMID: 41195166Schönfeld J, Liebisch N, Brunst S, Weizel L, Knapp S, Kannt A, Proschak E, Hiesinger K
Chem Commun (Camb). 2025-10-22 . .doi: 10.1039/d5cc03325j
PMID: 41120092Gotthardt G, Weckesser J, Tascher G, Barros da Gama S, Uckelmann HJ, Sun S, Schwalm MP, Mosler T, Ferrario G, Friedmann Angeli JP, Münch C, Knapp S, Müller S
EMBO Rep. 2025-10-17 . .doi: 10.1038/s44319-025-00593-4
PMID: 41102521Hoffmann L, Lenz C, Farges F, Kimani SW, Dopfer J, Keller S, Schwalm MP, Holzmann H, Kraemer A, Dong A, Li F, Chau I, Halabelian L, Gstaiger M, Müller S, Knapp S, Němec V
RSC Chem Biol. 2025-9-10 . .doi: 10.1039/d5cb00109a
PMID: 40927425Mensing TE, Kurz CG, Amrhein JA, Ehret TAL, Preuss F, Mathea S, Karim M, Tran DHN, Kadlecova Z, Tolvanen TA, Martinez-Molina D, Müller S, Einav S, Knapp S, Hanke T
Eur J Med Chem. 2025-8-30 . 299:118076 .doi: 10.1016/j.ejmech.2025.118076
PMID: 40882436Zhubi R, Chaikuad A, Muñoz Sosa CJ, Joerger AC, Knapp S
J Struct Biol X. 2025-8-18 . 12:100134 .doi: 10.1016/j.yjsbx.2025.100134
PMID: 40821731Hillebrand L, Wang G, Rasch A, Masberg B, Chaikuad A, Kronenberger T, Günther E, Forster M, Poso A, Lämmerhofer M, Laufer SA, Knapp S, Gehringer M
RSC Med Chem. 2025-8-4 . .doi: 10.1039/d5md00440c
PMID: 40756524Mandel S, Hanke T, Prendiville N, Baena-Nuevo M, Berger LM, Farges F, Schwalm MP, Berger BT, Kraemer A, Elson L, Saraswati H, Abdul Azeez KR, Dederer V, Mathea S, Corrionero A, Alfonso P, Keller S, Gstaiger M, Krause DS, Müller S, Röhm S, Knapp S
J Med Chem. 2025-7-2 . .doi: 10.1021/acs.jmedchem.5c01204
PMID: 40598933Schönfeld J, Brunst S, Ciomirtan L, Willmer L, Chromik MA, Kumar A, Froemel T, Liebisch N, Hackspacher A, Ehrler JHM, Wintermeier L, Hesse C, Fiedler J, Heering J, Freitag H, Zardo P, Fieguth HG, Brüggerhoff A, Jakob J, Häupl B, Weizel L, Kaiser A, Schubert-Zsilavecz M, Oellerich T, Fleming I, Schebb NH, Fürst R, Kannt A, Knapp S, Proschak E, Hiesinger K
J Med Chem. 2025-6-18 . .doi: 10.1021/acs.jmedchem.5c00552
PMID: 40532036