An Automated Microscale Thermophoresis Screening Approach for Fragment-Based Lead Discovery

Journal of Biomolecular Screening

Volumn 21, Issue 4, 2016, Pages 414-421

  Linke, Pawel ^a   Amaning, Kwame ^b   Maschberger, Melanie ^a   Vallee, Francois ^b   Steier, Valerie ^b   Baaske, Philipp ^a   Duhr, Stefan ^a   Breitsprecher, Dennis ^a   Rak, Alexey ^b  

^a NanoTemper Technologies GmbH   (Germany)

^b SANOFI   (France)

Author keywords

binding affinity; biophysical screening; drug discovery; protein aggregation; surface plasmon resonance

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; LIGAND; MAP2K1 PROTEIN, HUMAN; MOLECULAR LIBRARY; PROTEIN BINDING; PROTEIN KINASE INHIBITOR;

ARTICLE; AUTOMATED MICROSCALE THERMOPHORESIS; AUTOMATION; FRAGMENT BASED LEAD DISCOVERY; HIGH THROUGHPUT SCREENING; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DENATURATION; SIZE EXCLUSION CHROMATOGRAPHY; SURFACE PLASMON RESONANCE; THERMOSTABILITY; X RAY CRYSTALLOGRAPHY; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DEVICES; DIFFUSION; DRUG DEVELOPMENT; GENE EXPRESSION; HUMAN; MOLECULAR LIBRARY; MOLECULAR MODEL; PROCEDURES; TEMPERATURE;

CRYSTALLOGRAPHY, X-RAY; DIFFUSION; DRUG DISCOVERY; GENE EXPRESSION; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; LIGANDS; MAP KINASE KINASE 1; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN DENATURATION; PROTEIN KINASE INHIBITORS; SMALL MOLECULE LIBRARIES; SURFACE PLASMON RESONANCE; TEMPERATURE;

EID: 84961262682     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057115618347     Document Type: Article

References (15)

1. Baker M., Fragment-Based Lead Discovery Grows Up. Nat. Rev. Drug Discov. 2013, 12 (1), 5-7.
2. Kumar A., Voet A., Zhang K. Y., Fragment Based Drug Design: From Experimental to Computational Approaches. Curr. Med. Chem. 2012, 19 (30), 5128-5147.
3. Murray C. W., Rees D. C., The Rise of Fragment-Based Drug Discovery. Nat. Chem. 2009, 1 (3), 187-192.
4. Duhr S., Braun D., Why Molecules Move along a Temperature Gradient. Proc. Natl. Acad. Sci. U.S.A. 2006, 103 (52), 19678-19682.
5. Jerabek-Willemsen M., Andre T., Wanner R., et al. MicroScale Thermophoresis: Interaction Analysis and Beyond. J. Mol. Struct. 2014, 1077, 101-113.
6. Parker J. L., Newstead S., Molecular Basis of Nitrate Uptake by the Plant Nitrate Transporter NRT1.1. Nature 2014, 507 (7490), 68-72.
7. Radke M. B., Taft M. H., Stapel B., et al. Small Molecule-Mediated Refolding and Activation of Myosin Motor Function. eLife 2014, 3, e01603.
8. Hussein M., Bettio M., Schmitz A., et al. Cyplecksins Are Covalent Inhibitors of the Pleckstrin Homology Domain of Cytohesin. Angew. Chemie. Int. Ed. 2013, 52 (36), 9529-9533.
9. Mao Y., Yu L., Yang R., et al. A Novel Method for the Study of Molecular Interaction by Using Microscale Thermophoresis. Talanta 2015, 132 (0), 894-901.
10. Saini K. S., Loi S., de Azambuja E., et al. Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK Pathways in the Treatment of Breast Cancer. Cancer Treat. Rev. 2013, 39 (8), 935-946.
11. Amaning K., Lowinski M., Vallee F., et al. The Use of Virtual Screening and Differential Scanning Fluorimetry for the Rapid Identification of Fragments Active Against MEK1. Bioorg. Med. Chem. Lett. 2013, 23 (12), 3620-3626.
12. Smith C. K., Windsor W. T., Thermodynamics of Nucleotide and Non-ATP-Competitive Inhibitor Binding to MEK1 by Circular Dichroism and Isothermal Titration Calorimetry. Biochemistry 2007, 46 (5), 1358-1367.
13. Matulis D., Kranz J. K., Salemme F. R., et al. Thermodynamic Stability of Carbonic Anhydrase: Measurements of Binding Affinity and Stoichiometry Using ThermoFluor. Biochemistry 2005, 44 (13), 5258-5266.
14. Sheth P. R., Liu Y., Hesson T., et al. Fully Activated MEK1 Exhibits Compromised Affinity for Binding of Allosteric Inhibitors U0126 and PD0325901. Biochemistry 2011, 50 (37), 7964-7976.
15. McGovern S. L., Caselli E., Grigorieff N., et al. A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening. J. Med. Chem. 2002, 45 (8), 1712-1722.