Publications

At Proteros, we have assembled a world class team of 60 scientists.
So far, more than 250 peer reviewed publications of Proteros´ key scientists have been published.

2019
Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action Fournier, J. et al. Org Lett. 2019 Jan 10. doi: 10.1021/acs.orglett.8b03821 Abstract
Design and Evaluation of Highly Selective Human Immunoproteasome Inhibitors Reveal a Compensatory Process That Preserves Immune Cell Viability. Ladi, E. et al. J Med Chem. 2019 Aug 8;62(15):7032-7041. doi: 10.1021/acs.jmedchem.9b00509. Epub 2019 Jul 29. Abstract
Design of selective PI3Kδ inhibitors using an iterative scaffold-hopping workflow. Fradera, X. et al. Bioorg Med Chem Lett. 2019 Sep 15;29(18):2575-2580. doi: 10.1016/j.bmcl.2019.08.004. Epub 2019 Aug 5. Abstract
2018
Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer Ross B. et al. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1437-E1445. doi: 10.1073/pnas.1717565115. Epub 2018 Jan 30 Abstract
Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form Nelp M. T. et al. Proc Natl Acad Sci U S A. 2018 Mar 12. pii: 201719190. doi: 10.1073/pnas.1719190115 Abstract
A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors Vigolo M. et al. Nat Commun. 2018 Mar 23; 9(1):1199. doi: 10.1038/s41467-018-03323-8 Abstract
Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties Dyck B. et al. J Med Chem. 2017 Apr 27;60(8):3472-3483. doi: 10.1021/acs.jmedchem.7b00302. Epub 2017 Apr 13 Abstract
Enhancement of therapeutic potential of a naturally occurring human antibody targeting a phosphorylated Ser422 containing epitope on pathological tau van Ameidje, J. et al. Acta Neuropathol Commun. 2018 Jul 12;6(1):59. doi: 10.1186/s40478-018-0562-9. Abstract
Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo. Reuberson, J. et al. J Med Chem. 2018 Aug 9;61(15):6705-6723. doi: 10.1021/acs.jmedchem.8b00521. Epub 2018 Jul 19. Abstract
A common antigenic motif recognized by naturally occurring human VH5-51/VL4-1 anti-tau antibodies with distinct functionalities. Apetri, A. et al. Acta Neuropathol Commun. 2018 May 31;6(1):43. doi: 10.1186/s40478-018-0543-z. Abstract
β-Glucocerebrosidase Modulators Promote Dimerization of β-Glucocerebrosidase and Reveal an Allosteric Binding Site. Zheng, J. et al. J Am Chem Soc. 2018 May 9;140(18):5914-5924. doi: 10.1021/jacs.7b13003. Epub 2018 Apr 30. Abstract
The Y. bercovieri Anbu crystal structure sheds light on the evolution of highly (pseudo)symmetric multimers. Piesecka, A. et al. J Mol Biol. 2018 Mar 2;430(5):611-627. doi: 10.1016/j.jmb.2017.11.016. Epub 2017 Dec 16. Abstract
Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity Wei, B. et al J Med Chem. 2018 Feb 8;61(3):989-1000. doi: 10.1021/acs.jmedchem.7b01430. Epub 2017 Dec 21. Abstract
2017
Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition in Vivo. Lorthiois, E. et al. J Med Chem. 2017 Jul 13;60(13):5717-5735. doi: 10.1021/acs.jmedchem.7b00425. Epub 2017 Jun 30. Abstract
Structure-Based Design of Tricyclic NF-κB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K). Castanedo, GM. et al. J Med Chem. 2017 Jan 26;60(2):627-640. doi: 10.1021/acs.jmedchem.6b01363. Epub 2017 Jan 12. Abstract
2016
Discovery of a novel allosteric inhibitor-binding site in ERK5: comparison with the canonical kinase hinge ATP-binding site. Chen H., Tucker J., Wang X., Gavin P., Phillips C., Augustin M., Schreiner P., Steinbach S., Preston M., Ogg D. Acta Crystallogr D Struct Biol. 2016 May 1;72(Pt 5):682-93. doi: 10.1107/S2059798316004502. Epub 2016 Apr 26. Abstract
Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1. de Oliveira Mann CC, Kiefersauer R, Witte G, Hopfner KP. Sci Rep. 2016 Jun 8;6:27498. doi: 10.1038/srep27498. Abstract
Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors. Wagner, FF. et al. Bioorg Med Chem. 2016 Sep 15;24(18):4008-4015. doi: 10.1016/j.bmc.2016.06.040. Epub 2016 Jun 22. Abstract
Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8. Bergeron, P. et al. ACS Med Chem Lett. 2016 Apr 5;7(6):595-600. doi: 10.1021/acsmedchemlett.6b00044. eCollection 2016 Jun 9. Abstract
Development of a Potent, Specific CDK8 Kinase Inhibitor Which Phenocopies CDK8/19 Knockout Cells. Koehler, MF. et al. ACS Med Chem Lett. 2016 Jan 6;7(3):223-8. doi: 10.1021/acsmedchemlett.5b00278. eCollection 2016 Mar 10. Abstract
The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326). Heffron, TP. et al. J Med Chem. 2016 Feb 11;59(3):985-1002. doi: 10.1021/acs.jmedchem.5b01483. Epub 2016 Jan 20. Abstract
Identification of azabenzimidazoles as potent JAK1 selective inhibitors. Vasbinder, MM. et al. Bioorg Med Chem Lett. 2016 Jan 1;26(1):60-7. doi: 10.1016/j.bmcl.2015.11.031. Epub 2015 Nov 12. Abstract
2015
On-rate based optimization of structure–kinetic relationship – surfing the kinetic map Schoop, A. , Dey, F. (2015) Drug Discovery Today: Technologies, Vol. 17, Oct. 2015, Page 9-15 Abstract
Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization. Okamoto K, Ikemori-Kawada M, Jestel A, von König K, Funahashi Y, Matsushima T, Tsuruoka A, Inoue A, Matsui J. ACS Med Chem Lett. 2014 Nov 17;6(1):89-94. doi: 10.1021/ml500394m. eCollection 2015 Jan 8. Abstract
Molecular basis of in vitro affinity maturation and functional evolution of a neutralizing anti-human GM-CSF antibody. Eylenstein R., Weingärtner D., Härte S., Stromer R., Böttcher J., Augustin M., Ostendorf R., Steidl S. MAbs. 2016;8(1):176-86. doi: 10.1080/19420862.2015.1099774. Epub 2015 Sep 25. Abstract
Mediator Kinase Inhibition Further Activates Super-Enhancer Associated Genes in AML Henry E. Pelish et al. Nature. 2015 Oct 8; 526(7572): 273–276. doi: 10.1038/nature14904 Abstract
Data for the crystal structure of APRIL-BAFF-BAFF heterotrimer. Maskos, K. et al. Data Brief. 2015 Dec 18;6:438-44. doi: 10.1016/j.dib.2015.12.024. eCollection 2016 Mar. Abstract
Design, Synthesis, and Biological Evaluation of Quercetagetin Analogues as JNK1 Inhibitors. Hierold, J. et al. Chemistry. 2015 Nov 16;21(47):16887-94. doi: 10.1002/chem.201502475. Epub 2015 Oct 7. Abstract
Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging. Park, G. et al. Biochem Pharmacol. 2015 Dec 1;98(3):473-83. doi: 10.1016/j.bcp.2015.08.104. Epub 2015 Sep 2. Abstract
One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists. Schiebel, J. et al. ChemMedChem. 2015 Sep;10(9):1511-21. doi: 10.1002/cmdc.201500267. Epub 2015 Aug 10. Abstract
Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties. Schuepbach-Mallepell, S. et al. J Biol Chem. 2015 Jun 26;290(26):16330-42. doi: 10.1074/jbc.M115.661405. Epub 2015 May 7. Abstract
2014
IR laser-induced protein crystal transformation Kiefersauer, R. et al. (2014) Acta Cryst. Section D (2014) D70 Abstract
Structural analysis of the human fibroblast growth factor receptor 4 kinase. Leica E., Lammens A., Huber R., Augustin M. J Mol Biol. 2014 Nov 11;426(22):3744-56. doi: 10.1016/j.jmb.2014.09.004. Epub 2014 Sep 16. Abstract
Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization. Okamoto, K. et al. ACS Med Chem Lett. 2014 Nov 17;6(1):89-94. doi: 10.1021/ml500394m. eCollection 2015 Jan 8. Abstract
Structure-based optimization of non-peptidic Cathepsin D inhibitors. Grädler, U. et al. Bioorg Med Chem Lett. 2014 Sep 1;24(17):4141-50. doi: 10.1016/j.bmcl.2014.07.054. Epub 2014 Jul 25. Abstract
2013
Structural and functional analysis of the natural JNK1 inhibitor quercetagetin Baek, S. et al. (2013) J Mol Biol. 425, 411-23 Abstract
The E. coli effector protein NleF is a Caspase inhibitor Blasche, S. et al. (2013) PLoS One. 8, 58937 Abstract
Discovery and optimization of a novel series of potent mutant B-Raf V600E selective kinase inhibitors Vasbinder, M.M., et al. (2013) J Med Chem. 56, 1996-2015 Abstract
Structure-Kinetic-Relationship study of CDK8/CycC specific compounds Schneider, E.V. et al.(2013) Proc Natl Acad Sci USA. 110, 8081-6 Abstract
Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability Lauffer, B.E.L. et al.(2013) J Biol Chem. 288, 26926-43 Abstract
2012
Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin k inhibitors Crawford, J.J. et al.(2012) J Med Chem. 55, 8827-37 Abstract
Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition Dossetter, A.G. et al.(2012) Bioorg Med Chem Lett. 22, 5563-8 Abstract
(1R,2R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): a potent and highly selective cathepsin K inhibitor for the treatment of osteoarthritis Dossetter, A.G. et al. (2012) J Med Chem. 55, 6363-74 Abstract
High-resolution crystal structures of factor XIa coagulation factor in complex with nonbasic high-affinity synthetic inhibitors Fradera, X. et al.(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun. 68, 404-8 Abstract
2011
HTS reporter displacement assay for fragment screening and fragment evolution toward leads with optimized binding kinetics, binding selectivity, and thermodynamic signature Neumann, L. et al.(2011) Methods Enzymol. 493, 299-320 Abstract
The structure of CDK8/CycC implicates specificity in the CDK/Cyclin family and reveals interaction with a deep pocket binder Schneider, E.V. et al.(2011) J Mol Biol. 412, 251-266 Abstract
Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers Gerritz, S.W. et al. (2011) Proc Natl Acad Sci USA. 108, 15366-71 Abstract
Key factors for successful generation of protein-fragment structures requirement on protein, crystals, and technology Böttcher, J. et al.(2011) Methods Enzymol. 493, 61-89 Abstract
An old NSAID revisited: crystal structure of aldose reductase in complex with sulindac at 1.0 Å supports a novel mechanism for its anticancer and antiproliferative effects. Steuber, H. et al. ChemMedChem. 2011 Dec 9;6(12):2155-7. doi: 10.1002/cmdc.201100374. Epub 2011 Oct 13. Abstract
2010
The ‘retro-design’ concept for novel kinase inhibitors Müller, G. et al.(2010) IDrugs. 13, 457-66 Abstract
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions Buttar, D. et al.(2010) Bioorg Med Chem. 18, 7486-7496 Abstract
The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis Wang, J. et al. (2010) Biochemistry. 49, 7972-4 Abstract
2009
Fragment-based discovery of BACE1 inhibitors using functional assays Godemann, R. et al.(2009) Biochemistry. 48, 10743-51 Abstract
Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology Neumann, L. et al.(2009) J Comput Aided Mol Des. 23, 501-11 Abstract
Dipeptidyl nitrile inhibitors of Cathepsin L Asaad, N. et al. (2009) Bioorg Med Chem Lett. 19, 4280-4283 Abstract
Design of selective Cathepsin inhibitors Bethel, P.A. et al.(2009) Bioorg Med Chem Lett. 19, 4622-5 Abstract
Structural and functional studies of the yeast class II Hda1 histone deacetylase complex Lee, J.H. et al.(2009) J Mol Biol. 391, 744-57 Abstract
2008
Phosphorylation of the human full-length protein kinase C-iota Macek, B. et al.(2008) J Proteome Res. 7, 2928-35 Abstract
2007
Macrocyclic statine-based inhibitors of BACE-1 Barazza, A. et al.(2007) Chembiochem. 8, 2078-91 Abstract
2005
Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif Messerschmidt, A. et al.(2005) J Mol Biol. 352, 918-931 Abstract
Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor Roehrig S. er al.(2005) J Med Chem. 48, 5900-8 Abstract