Computational Discovery and Experimental Confirmation of TLR9 Receptor Antagonist Leads

Journal of Chemical Information and Modeling

Volumn 56, Issue 9, 2016, Pages 1835-1846

  Zatsepin, Maria ^a   Mattes, Angela ^b   Rupp, Steffen ^b   Finkelmeier, Doris ^b   Basu, Arijit ^a   Burger Kentischer, Anke ^b   Goldblum, Amiram ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b FRAUNHOFER INSTITUTE FOR INTERFACIAL ENGINEERING AND BIOTECHNOLOGY IGB   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; COMPUTATIONAL CHEMISTRY; ITERATIVE METHODS; PATTERN RECOGNITION SYSTEMS; PHYSICOCHEMICAL PROPERTIES; PLANTS (BOTANY); STOCHASTIC MODELS; STOCHASTIC SYSTEMS;

ANTAGONISTIC ACTIVITY; CHRONIC INFLAMMATORY; EXPERIMENTAL CONFIRMATION; HUMAN PATTERN RECOGNITION; PATHOGEN-ASSOCIATED MOLECULAR PATTERNS; RECEPTOR ANTAGONISTS; THERAPEUTIC INTERVENTION; TOLL-LIKE RECEPTORS;

MOLECULES;

TOLL LIKE RECEPTOR 9;

ALGORITHM; ANIMAL; ANTAGONISTS AND INHIBITORS; COMPUTER SIMULATION; DRUG DEVELOPMENT; HIGH THROUGHPUT SCREENING; HUMAN; IC50; MARKOV CHAIN; MATERIALS TESTING; MOUSE; NIH 3T3 CELL LINE; PROCEDURES;

ALGORITHMS; ANIMALS; COMPUTER SIMULATION; DRUG DISCOVERY; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; MATERIALS TESTING; MICE; NIH 3T3 CELLS; STOCHASTIC PROCESSES; TOLL-LIKE RECEPTOR 9;

EID: 84988905494     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/acs.jcim.6b00070     Document Type: Article

References (34)

1. Beutler, B. Innate Immunity: An Overview Mol. Immunol. 2004, 40, 845-859 10.1016/j.molimm.2003.10.005
2. Botos, I.; Segal, D. M.; Davies, D. R. The Structural Biology of Toll-like Receptors Structure 2011, 19, 447-459 10.1016/j.str.2011.02.004
3. Akira, S.; Takeda, K. Toll-like Receptor Signalling Nat. Rev. Immunol. 2004, 4, 499-511 10.1038/nri1391
4. Burger-Kentischer, A.; Abele, I. S.; Finkelmeier, D.; Wiesmüller, K.-H.; Rupp, S. A New Cell-based Innate Immune Receptor Assay for the Examination of Receptor Activity, Ligand Specificity, Signalling Pathways and the Detection of Pyrogens J. Immunol. Methods 2010, 358, 93-103 10.1016/j.jim.2010.03.020
5. Americn Chemical Society Computers in ChemistryDivisionSymposium on Emerging Computational Technologies August (2000, Washington D.C. http://oldwww.acscomp.org/Awards/emerging2000.html (accessed August 29, 2016).
6. Stern, N.; Goldblum, A. Iterative Stochastic Elimination for Solving Complex Combinatorial Problems in Drug Discovery Isr. J. Chem. 2014, 54, 1338-1357 10.1002/ijch.201400072
7. Hari, A.; Flach, T. L.; Shi, Y.; Mydlarski, P. R. Toll-like Receptors: Role in Dermatological Disease Mediators Inflammation 2010, 2010, 1 10.1155/2010/437246
8. Plitas, G.; Burt, B. M.; Nguyen, H. M.; Bamboat, Z. M.; DeMatteo, R. P. Toll-like Receptor 9 Inhibition Reduces Mortality in Polymicrobial Sepsis J. Exp. Med. 2008, 205, 1277-1283 10.1084/jem.20080162
9. Luisa, G. M.; Murciano, C.; Yanez, A.; Gozalbo, D. Role of Toll-like receptors in Systemic Candida albicans Infections Front. Biosci., Landmark Ed. 2016, 21, 278-302 10.2741/4388
10. Kanzler, H.; Barrat, F. J.; Hessel, E. M.; Coffman, R. L. Therapeutic Targeting of Innate Immunity with Toll-like Receptor Agonists and Antagonists Nat. Med. 2007, 13, 552-559 10.1038/nm1589
11. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242 10.1093/nar/28.1.235
12. Wlodawer, A.; Vondrasek, J. Inhibitors of HIV-1 Protease: A Major Success of Structure-assisted Drug Design 1 Annu. Rev. Biophys. Biomol. Struct. 1998, 27, 249-284 10.1146/annurev.biophys.27.1.249
13. Zhou, W.; Li, Y.; Pan, X.; Gao, Y.; Li, B.; Qiu, Z.; Liang, L.; Zhou, H.; Yue, J. Toll-like Receptor 9 Interaction with CpG ODN-An In Silico Analysis Approach Theor. Biol. Med. Modell. 2013, 10, 18 10.1186/1742-4682-10-18
14. Stahura, F. L.; Bajorath, J. New Methodologies for Ligand-based Virtual Screening Curr. Pharm. Des. 2005, 11, 1189-1202 10.2174/1381612053507549
15. Baldi, P.; Brunak, S.; Chauvin, Y.; Andersen, C. A.; Nielsen, H. Assessing the Accuracy of Prediction Algorithms for Classification: An Overview Bioinformatics 2000, 16, 412-424 10.1093/bioinformatics/16.5.412
16. Glick, M.; Rayan, A.; Goldblum, A. A Stochastic Algorithm for Global Optimization and for Best Populations: A Test Case of Side Chains in Proteins Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 703-708 10.1073/pnas.022418199
17. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B. et al. ChEMBL: A Large-scale Bioactivity Database for Drug Discovery Nucleic Acids Res. 2012, 40, D1100-D1107 10.1093/nar/gkr777
18. Czarniecki, M. Small Molecule Modulators of Toll-like Receptors J. Med. Chem. 2008, 51, 6621-6626 10.1021/jm800957k
19. Wang, Y.; Xiao, J.; Suzek, T. O.; Zhang, J.; Wang, J.; Zhou, Z.; Han, L.; Karapetyan, K.; Dracheva, S.; Shoemaker, B. A. et al. PubChem's BioAssay Database Nucleic Acids Res. 2012, 40, D400-D412 10.1093/nar/gkr1132
20. Zheng, W.; Spyvee, M.; Gusovsky, F.; Ishizaka, S. T. Benzoxazole derivatives as immune toll-like receptor stimulators and their preparation, pharmaceutical compositions and use in the treatment of immunological disorders. WO 2010/036905, 2010.
21. Lipford, G.; Forsbach, A.; Zepp, C. Small molecule toll-like receptor (TLR) antagonists. WO 2005/007672, 2005.
22. Lippford, G. B.; Zepp, C. M.; Nguyen, T. B. Benzoxazole derivatives as immune toll-like receptor stimulators and their preparation, pharmaceutical compositions and use in the treatment of immunological disorders. WO 2008/030455, 2008.
23. Molecular Operating Environment (MOE), 2013.08; Chemical Computing Group Inc.: Montreal, QC, Canada, 2013.
24. Enamine Ltd. Screening compound Provider. http://www.enamine.net/ 2015, (accessed August 29, 2016).
25. Virtual Computational Chemistry Laboratory VCCLAB: ALOGPS 2.1 Software, Neuherberg (Munich), 2005, http://www.vcclab.org/lab/alogps/ (accessed August 29, 2016).
26. Laboratory of Molecular Modeling and Design (LMMD): admetSAR tool Software, http://lmmd.ecust.edu.cn/ (accessed August 29, 2016).
27. Wang, J.; Krudy, G.; Hou, T.; Zhang, W.; Holland, G.; Xu, X. Development of Reliable Aqueous Solubility Models and Their Application in Druglike Analysis J. Chem. Inf. Model. 2007, 47, 1395-1404 10.1021/ci700096r
28. SciFinder Scholar http://www.cas.org/products/scifinder (accessed August 29, 2016).
29. Ohto, U.; Shibata, T.; Tanji, H.; Ishida, H.; Krayukhina, E.; Uchiyama, S.; Miyake, K.; Shimizu, T. Structural Basis of CpG and Inhibitory DNA Recognition by Toll-like Receptor 9 Nature 2015, 520, 702-705 10.1038/nature14138
30. Nothelfer, K.; Arena, E. T.; Pinaud, L.; Neunlist, M.; Mozeleski, B.; Belotserkovsky, I.; Parsot, C.; Dinadayala, P.; Burger-Kentischer, A.; Raqib, R. et al. B Lymphocytes Undergo TLR2-Dependent Apoptosis upon Shigella Infection J. Exp. Med. 2014, 211, 1215-1229 10.1084/jem.20130914
31. Krieg, A. M.; Yi, A.-K.; Matson, S.; Waldschmidt, T. J.; Bishop, G. A.; Teasdale, R.; Koretzky, G. A.; Klinman, D. M. CpG Motifs in Bacterial DNA Trigger Direct B-cell Activation Nature 1995, 374, 546-549 10.1038/374546a0
32. Matthews, B. W. Comparison of the predicted and observed secondary structure of T4 phage lysozyme Biochim. Biophys. Acta, Protein Struct. 1975, 405, 442-451 10.1016/0005-2795(75)90109-9
33. Posner, B. A.; Xi, H.; Mills, J. E. J. Enhanced HTS Hit Selection via a Local Hit Rate Analysis J. Chem. Inf. Model. 2009, 49, 2202-2210 10.1021/ci900113d
34. Willett, P. Similarity-based Virtual Screening Using 2D Fingerprints Drug Discovery Today 2006, 11, 1046-1053 10.1016/j.drudis.2006.10.005