Structure Gallery
Here you can find the whole collection of structures that have been published by the Rauh Lab.
Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA.
Teuber, A., Schulz, T., Fletcher, B.S., Gontla, R., Muhlenberg, T., Zischinsky, M.L., Niggenaber, J., Weisner, J., Kleinbolting, S.B., Lategahn, J., Sievers, S., Muller, M.P., Bauer, S., Rauh, D.
(2024) Nat Commun 15: 63-63
PubMed Article: 38167404
View in pdb database: 8PQ9 8PQA 8PQB 8PQC 8PQD 8PQE 8PQF 8PQG 8PQH 8PQI 8PQJ 8PQK
Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp 3 -Enriched Fragment Library.
Buhrmann, M., Kallepu, S., Warmuth, J.D., Wiese, J.N., Ehrt, C., Vatheuer, H., Hiller, W., Seitz, C., Levy, L., Czodrowski, P., Sievers, S., Muller, M.P., Rauh, D.
(2023) J Med Chem 66: 6297-6314
PubMed Article: 37130057
View in pdb database: 8C6P 8C6Q 8C6S 8C6T 8C70 8C71 8C72 8C74
Addressing the Osimertinib Resistance Mutation EGFR-L858R/C797S with Reversible Aminopyrimidines.
Grabe, T., Jeyakumar, K., Niggenaber, J., Schulz, T., Koska, S., Kleinbolting, S., Beck, M.E., Muller, M.P., Rauh, D.
(2023) ACS Med Chem Lett 14: 591-598
PubMed Article: 37197473
Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors.
Goebel, L., Kirschner, T., Koska, S., Rai, A., Janning, P., Maffini, S., Vatheuer, H., Czodrowski, P., Goody, R.S., Muller, M.P., Rauh, D.
(2023) Elife 12
PubMed Article: 36972177
Optimization of Covalent MKK7 Inhibitors via Crude Nanomole-Scale Libraries.
Gehrtz, P., Marom, S., Buhrmann, M., Hardick, J., Kleinbolting, S., Shraga, A., Dubiella, C., Gabizon, R., Wiese, J.N., Muller, M.P., Cohen, G., Babaev, I., Shurrush, K., Avram, L., Resnick, E., Barr, H., Rauh, D., London, N.
(2022) J Med Chem 65: 10341-10356
PubMed Article: 35912476
Insight into Targeting Exon20 Insertion Mutations of the Epidermal Growth Factor Receptor with Wild Type-Sparing Inhibitors.
Lategahn, J., Tumbrink, H.L., Schultz-Fademrecht, C., Heimsoeth, A., Werr, L., Niggenaber, J., Keul, M., Parmaksiz, F., Baumann, M., Menninger, S., Zent, E., Landel, I., Weisner, J., Jeyakumar, K., Heyden, L., Russ, N., Muller, F., Lorenz, C., Bragelmann, J., Spille, I., Grabe, T., Muller, M.P., Heuckmann, J.M., Klebl, B.M., Nussbaumer, P., Sos, M.L., Rauh, D.
(2022) J Med Chem 65: 6643-6655
PubMed Article: 35486541
Insights into the binding of pyrazolopyrimidines to Src kinase.
Dello Iacono, L., Kleinboelting, S., Passannanti, R., Fallacara, A.L., Di Pisa, F., Richters, A., Musumeci, F., Rauh, D., Schenone, S., Botta, M.
To be published
View in pdb database: 7AH3
Cellular model system to dissect the isoform-selectivity of Akt inhibitors.
Quambusch, L., Depta, L., Landel, I., Lubeck, M., Kirschner, T., Nabert, J., Uhlenbrock, N., Weisner, J., Kostka, M., Levy, L.M., Schultz-Fademrecht, C., Glanemann, F., Althoff, K., Muller, M.P., Siveke, J.T., Rauh, D.
(2021) Nat Commun 12: 5297-5297
PubMed Article: 34489430
Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands.
Niggenaber, J., Heyden, L., Grabe, T., Muller, M.P., Lategahn, J., Rauh, D.
(2020) ACS Med Chem Lett 11: 2484-2490
PubMed Article: 33335671
Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach.
Lategahn, J., Hardick, J., Grabe, T., Niggenaber, J., Jeyakumar, K., Keul, M., Tumbrink, H.L., Becker, C., Hodson, L., Kirschner, T., Klovekorn, P., Ketzer, J., Baumann, M., Terheyden, S., Unger, A., Weisner, J., Muller, M.P., van Otterlo, W.A.L., Bauer, S., Rauh, D.
(2020) J Med Chem
PubMed Article: 32931277
Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S.
Lategahn, J., Keul, M., Klovekorn, P., Tumbrink, H.L., Niggenaber, J., Muller, M.P., Hodson, L., Flasshoff, M., Hardick, J., Grabe, T., Engel, J., Schultz-Fademrecht, C., Baumann, M., Ketzer, J., Muhlenberg, T., Hiller, W., Gunther, G., Unger, A., Muller, H., Heimsoeth, A., Golz, C., Blank-Landeshammer, B., Kollipara, L., Zahedi, R.P., Strohmann, C., Hengstler, J.G., van Otterlo, W.A.L., Bauer, S., Rauh, D.
(2019) Chem Sci 10: 10789-10801
PubMed Article: 31857889
Covalent-Allosteric Inhibitors to Achieve Akt Isoform-Selectivity.
Quambusch, L., Landel, I., Depta, L., Weisner, J., Uhlenbrock, N., Muller, M.P., Glanemann, F., Althoff, K., Siveke, J.T., Rauh, D.
(2019) Angew Chem Int Ed Engl 58: 18823-18829
PubMed Article: 31584233
Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).
Wolle, P., Engel, J., Smith, S., Goebel, L., Hennes, E., Lategahn, J., Rauh, D.
(2019) J Med Chem 62: 5541-5546
PubMed Article: 31083997
2-Azo-, 2-diazocine-thiazols and 2-azo-imidazoles as photoswitchable kinase inhibitors: limitations and pitfalls of the photoswitchable inhibitor approach.
Schehr, M., Ianes, C., Weisner, J., Heintze, L., Muller, M.P., Pichlo, C., Charl, J., Brunstein, E., Ewert, J., Lehr, M., Baumann, U., Rauh, D., Knippschild, U., Peifer, C., Herges, R.
(2019) Photochem Photobiol Sci 18: 1398-1407
PubMed Article: 30924488
Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-mutant Pancreatic and Colorectal Cancer.
Weisner J., Landel I., Reintjes C., Uhlenbrock N., Trajkovic-Arsic M., Dienstbier N., Hardick J., Ladigan S., Lindemann M., Smith S., Quambusch L., Scheinpflug R., Depta L., Gontla R., Unger A., Müller H., Baumann M., Schultz-Fademrecht C., Günther G., Maghnouj A., Müller M.P., Pohl M., Teschendorf C., Wolters H., Viebahn R., Tannapfel A., Uhl W., Hengstler J.G., Hahn S.A., Siveke J.T., Rauh D.
(2019) Cancer Res
Pubmed Article: 30858154
View in pdb database: 6HHF
Co-crystal structure determination and cellular evaluation of 1,4-dihydropyrazolo[4,3-c] [1,2] benzothiazine 5,5-dioxide p38α MAPK inhibitors.
Bartolini D., Bührmann M., Barreca M.L., Manfroni G., Cecchetti V., Rauh D., Galli F.
(2019) Biochem Biophys Res Commun
Pubmed Article: 30824186
Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors.
Wolle P., Hardick J., Cronin S.J.F., Engel J., Baumann M., Lategahn J., Penninger J.M., Rauh D.
(2019) J Med Chem
Pubmed Article: 30768270
Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt.
Uhlenbrock, N., Smith, S., Weisner, J., Landel, I., Lindemann, M., Le, T.A., Hardick, J., Gontla, R., Scheinpflug, R., Czodrowski, P., Janning, P., Depta, L., Quambusch, L., Muller, M.P., Engels, B., Rauh, D.
(2019) Chem Sci 10: 3573-3585
PubMed Article: 30996949
An Unusual Intramolecular Halogen Bond guides Conformational Selection.
Tesch R., Becker C., Müller M.P., Beck M.E., Quambusch L., Getlik M., Lategahn J., Uhlenbrock N., Costa F.N., Polêto M.D., de Sena Murteira Pinheiro P., Rodrigues D.A., Sant'Anna C.M., Ferreira F.F., Verli H., Fraga C.A.M., Rauh D.
(2018) Angew Chem Int Ed Engl
Pubmed Article: 29873877
View in pdb database: 6GN1
Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK.
Bührmann M., Wiedemann B.M., Müller M.P., Hardick J., Ecke M., Rauh D.
(2017) PLoS One 12: e0184627
Pubmed Article: 28892510
Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine.
Walter N.M., Wentsch H.K., Bührmann M., Bauer S.M., Döring E., Mayer-Wrangowski S., Sievers-Engler A., Willemsen-Seegers N., Zaman G., Buijsman R., Lämmerhofer M., Rauh D., Laufer S.A.
(2017) J Med Chem 60: 8027-8054
Pubmed Article: 2883
Covalent Lipid Pocket Ligands Targeting p38α MAPK Mutants.
Bührmann M., Hardick J., Weisner J., Quambusch L., Rauh D.
(2017) Angew Chem Int Ed Engl 56: 13232-13236
Pubmed Article: 28834017
Optimized Target Residence Time: Type I1/2 Inhibitors for p38α MAP Kinase with Improved Binding Kinetics through Direct Interaction with the R-Spine.
Wentsch H.K., Walter N.M., Bührmann M., Mayer-Wrangowski S., Rauh D., Zaman G.J.R., Willemsen-Seegers N., Buijsman R.C., Henning M., Dauch D., Zender L., Laufer S.
(2017) Angew Chem Int Ed Engl 56: 5363-5367
Pubmed Article: 28397331
Optimized 4,5-Diarylimidazoles as Potent/Selective Inhibitors of Protein Kinase CK1δ and Their Structural Relation to p38α MAPK.
Halekotte J., Witt L., Ianes C., Krüger M., Bührmann M., Rauh D., Pichlo C., Brunstein E., Luxenburger A., Baumann U., Knippschild U., Bischof J., Peifer C.
(2017) Molecules 22: null
Pubmed Article: 28338621
Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR.
Engel J., Becker C., Lategahn J., Keul M., Ketzer J., Mühlenberg T., Kollipara L., Schultz-Fademrecht C., Zahedi R.P., Bauer S., Rauh D.
(2016) Angew Chem Int Ed Engl 55: 10909-12
Pubmed Article: 27496389
Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach.
Engel J., Richters A., Getlik M., Tomassi S., Keul M., Termathe M., Lategahn J., Becker C., Mayer-Wrangowski S., Grütter C., Uhlenbrock N., Krüll J., Schaumann N., Eppmann S., Kibies P., Hoffgaard F., Heil J., Menninger S., Ortiz-Cuaran S., Heuckmann J.M., Tinnefeld V., Zahedi R.P., Sos M.L., Schultz-Fademrecht C., Thomas R.K., Kast S.M., Rauh D.
(2015) J Med Chem 58: 6844-63
Pubmed Article: 26275028
Neuritogenic militarinone-inspired 4-hydroxypyridones target the stress pathway kinase MAP4K4.
Schröder P., Förster T., Kleine S., Becker C., Richters A., Ziegler S., Rauh D., Kumar K., Waldmann H.
(2015) Angew Chem Int Ed Engl 54: 12398-403
Pubmed Article: 25908259
View in pdb database: 4RVT
Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo[3,4-d]pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma.
Tintori C., Fallacara A.L., Radi M., Zamperini C., Dreassi E., Crespan E., Maga G., Schenone S., Musumeci F., Brullo C., Richters A., Gasparrini F., Angelucci A., Festuccia C., Delle Monache S., Rauh D., Botta M.
(2015) J Med Chem 58: 347-61
Pubmed Article: 25469771
View in pdb database: 4O2P
Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues.
Tziridis A., Rauh D., Neumann P., Kolenko P., Menzel A., Bräuer U., Ursel C., Steinmetzer P., Stürzebecher J., Schweinitz A., Steinmetzer T., Stubbs M.T.
(2014) Biol Chem 395: 891-903
Pubmed Article: 25003390
View in pdb database: 3PLB 3V13 3V12 3UY9 3UWI 3UUZ 3UQV 3UQO 3UPE 3UOP 3UNS 3UNQ 3Q00 3PYH 3PWC 3PWB 3PMJ 3PM3 3PLP 3PLK
Metabolically stable dibenzo[b,e]oxepin-11(6H)-ones as highly selective p38 MAP kinase inhibitors: optimizing anti-cytokine activity in human whole blood.
Baur B., Storch K., Martz K.E., Goettert M.I., Richters A., Rauh D., Laufer S.A.
(2013) J Med Chem 56: 8561-78
Pubmed Article: 24131218
View in pdb database: 4L8M
Structural characterization of the RLCK family member BSK8: a pseudokinase with an unprecedented architecture.
Grütter C., Sreeramulu S., Sessa G., Rauh D.
(2013) J Mol Biol 425: 4455-67
Pubmed Article: 23911552
De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments.
Urich R., Wishart G., Kiczun M., Richters A., Tidten-Luksch N., Rauh D., Sherborne B., Wyatt P.G., Brenk R.
(2013) ACS Chem Biol 8: 1044-52
Pubmed Article: 23534475
View in pdb database: 4FIC
Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity.
Fischer S., Wentsch H.K., Mayer-Wrangowski S.C., Zimmermann M., Bauer S.M., Storch K., Niess R., Koeberle S.C., Grütter C., Boeckler F.M., Rauh D., Laufer S.A.
(2013) J Med Chem 56: 241-53
Pubmed Article: 23270382
View in pdb database: 3UVQ
Natural-product-derived fragments for fragment-based ligand discovery.
Over B., Wetzel S., Grütter C., Nakai Y., Renner S., Rauh D., Waldmann H.
(2013) Nat Chem 5: 21-8
Pubmed Article: 23247173
View in pdb database: 4EH2 4EHV 4EH9 4EH8 4EH7 4EH6 4EH5 4EH4 4EH3
Targeting the hinge glycine flip and the activation loop: novel approach to potent p38α inhibitors.
Martz K.E., Dorn A., Baur B., Schattel V., Goettert M.I., Mayer-Wrangowski S.C., Rauh D., Laufer S.A.
(2012) J Med Chem 55: 7862-74
Pubmed Article: 22897496
View in pdb database: 3UVP
Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase.
Getlik M., Simard J.R., Termathe M., Grütter C., Rabiller M., van Otterlo W.A., Rauh D.
(2012) PLoS One 7: e39713
Pubmed Article: 22768308
Overcoming Gatekeeper Mutations in cSrc and Abl by Hybrid Compound Design.
Richters, A., Getlik, M., Gruetter, C., Schneider, R., Heuckmann, J.M., Heynck, S., Sos, M.L., Thomas, R.K., Rauh, D.
To be published
Targeting GSK3 from Ustilago maydis: type-II kinase inhibitors as potential antifungals.
Grütter C., Simard J.R., Mayer-Wrangowski S.C., Schreier P.H., Pérez-Martín J., Richters A., Getlik M., Gutbrod O., Braun C.A., Beck M.E., Rauh D.
(2012) ACS Chem Biol 7: 1257-67
Pubmed Article: 22545924
View in pdb database: 4E7W
Resolving the selectivity problem for p38 mitogen activated protein (MAP) Kinase-inhibitors: Development of new highly potent inhibitors of p38 MAP kinase with an outstanding selectivity profile.
Karcher, S.C., Fischer, S., Schattel, V., Romir, J., Stehle, T., Gruetter, C., Rauh, D., Laufer, S.A.
To be published
View in pdb database: 3QUD
Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor.
Koeberle S.C., Romir J., Fischer S., Koeberle A., Schattel V., Albrecht W., Grütter C., Werz O., Rauh D., Stehle T., Laufer S.A.
(2011) Nat Chem Biol 8: 141-3
Pubmed Article: 22198732
Structure-based design and synthesis of cell active N-pyrazole, N-thiazole urea inhibitors of the MAP kinase p38alpha.
Getlik, M., Gruetter, C., Simard, J.R., Van Otterlo, W., Robubi, A., Aust, B., Rauh, D.
To be published
View in pdb database: 3PG3
Development of novel thiazole-urea compounds which stabalize the inactive conformation of p38 alpha.
Getlik, M., Gruetter, C., Simard, J.R., Van Otterlo, W., Robubi, A., Aust, B., Rauh, D
To be published
Identification of Ustilago maydis Aurora kinase as a novel antifungal target.
Tückmantel S., Greul J.N., Janning P., Brockmeyer A., Grütter C., Simard J.R., Gutbrod O., Beck M.E., Tietjen K., Rauh D., Schreier P.H.
(2011) ACS Chem Biol 6: 926-33
Pubmed Article: 21671622
View in pdb database: 3QBN
Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance.
Klüter S., Simard J.R., Rode H.B., Grütter C., Pawar V., Raaijmakers H.C., Barf T.A., Rabiller M., van Otterlo W.A., Rauh D.
(2010) Chembiochem 11: 2557-66
Pubmed Article: 21080395
View in pdb database: 3LOK
Fluorophore labeling of the glycine-rich loop as a method of identifying inhibitors that bind to active and inactive kinase conformations.
Simard J.R., Getlik M., Grütter C., Schneider R., Wulfert S., Rauh D.
(2010) J Am Chem Soc 132: 4152-60
Pubmed Article: 20201574
Displacement assay for the detection of stabilizers of inactive kinase conformations.
Klüter S., Grütter C., Naqvi T., Rabiller M., Simard J.R., Pawar V., Getlik M., Rauh D.
(2010) J Med Chem 53: 357-67
Pubmed Article: 19928858
High-throughput screening to identify inhibitors which stabilize inactive kinase conformations in p38alpha.
Simard J.R., Grütter C., Pawar V., Aust B., Wolf A., Rabiller M., Wulfert S., Robubi A., Klüter S., Ottmann C., Rauh D.
(2009) J Am Chem Soc 131: 18478-88
Pubmed Article: 19950957
Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors.
Simard J.R., Getlik M., Grütter C., Pawar V., Wulfert S., Rabiller M., Rauh D.
(2009) J Am Chem Soc 131: 13286-96
Pubmed Article: 19572644
Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc.
Getlik M., Grütter C., Simard J.R., Klüter S., Rabiller M., Rode H.B., Robubi A., Rauh D.
(2009) J Med Chem 52: 3915-26
Pubmed Article: 19462975
A new screening assay for allosteric inhibitors of cSrc.
Simard J.R., Klüter S., Grütter C., Getlik M., Rabiller M., Rode H.B., Rauh D.
(2009) Nat Chem Biol 5: 394-6
Pubmed Article: 19396179
Human carbonyl reductase 1 is an S-nitrosoglutathione reductase.
Bateman R.L., Rauh D., Tavshanjian B., Shokat K.M.
(2008) J Biol Chem 283: 35756-62
Pubmed Article: 18826943
Biochemical and structural analysis of substrate promiscuity in plant Mg2+-dependent O-methyltransferases.
Kopycki J.G., Rauh D., Chumanevich A.A., Neumann P., Vogt T., Stubbs M.T.
(2008) J Mol Biol 378: 154-64
Pubmed Article: 18342334
View in pdb database: 3C3Y
Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR.
Michalczyk A., Klüter S., Rode H.B., Simard J.R., Grütter C., Rabiller M., Rauh D.
(2008) Bioorg Med Chem 16: 3482-8
Pubmed Article: 18316192
Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct.
Bateman R., Rauh D., Shokat K.M.
(2007) Org Biomol Chem 5: 3363-7
Pubmed Article: 17912391
View in pdb database: 2PFG
Structure-guided development of affinity probes for tyrosine kinases using chemical genetics.
Blair J.A., Rauh D., Kung C., Yun C.H., Fan Q.W., Rode H., Zhang C., Eck M.J., Weiss W.A., Shokat K.M.
(2007) Nat Chem Biol 3: 229-38
Pubmed Article: 17334377
Structure and properties of a re-engineered homeodomain protein-DNA interface.
Simon M.D., Feldman M.E., Rauh D., Maris A.E., Wemmer D.E., Shokat K.M.
(2006) ACS Chem Biol 1: 755-60
Pubmed Article: 17240973
An unbiased cell morphology-based screen for new, biologically active small molecules.
Tanaka M., Bateman R., Rauh D., Vaisberg E., Ramachandani S., Zhang C., Hansen K.C., Burlingame A.L., Trautman J.K., Shokat K.M., Adams C.L.
(2005) PLoS Biol 3: e128
Pubmed Article: 15799708
View in pdb database: 1WMA
