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Review

Mechanism of Action Assays for Enzymes

John Strelow, Walthere Dewe, Phillip W Iversen  1 , Harold B Brooks, Jeffrey A Radding, James McGee  1 , Jeffrey Weidner  2
Sarine Markossian  1 , Abigail Grossman  1 , Hannah Baskir  1 , Michelle Arkin  2 , Douglas Auld  3 , Christopher Austin  4 , Jonathan Baell  5 , Kyle Brimacombe  1 , Thomas D.Y. Chung  6 , Nathan P. Coussens  7 , Jayme L. Dahlin  8 , Viswanath Devanarayan  9 , Timothy L. Foley  10 , Marcie Glicksman  11 , Kirill Gorshkov  12 , Stefan Grotegut  13 , Matthew D. Hall  1 , Samuel Hoare  14 , James Inglese  1 , Philip W. Iversen  15 , Madhu Lal-Nag  16 , Zhuyin Li  12 , Jason R. Manro  13 , James McGee  17 , Allison Norvil  13 , Mackenzie Pearson  13 , Terry Riss  18 , Peter Saradjian  19 , G. Sitta Sittampalam  20 , Michael A. Tarselli  21 , O. Joseph Trask Jr.  22 , Jeffrey R. Weidner  23 , Mary Jo Wildey  24 , Kelli Wilson  1 , Menghang Xia  1 , Xin Xu  1
, editors.
In: Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004.
[updated ].
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Free Books & Documents
Review

Mechanism of Action Assays for Enzymes

John Strelow et al.
Free Books & Documents

Excerpt

Many drugs are inhibitors of enzymes involved in mediating the disease processes. Understanding the mechanism of action (MOA) of the target enzyme is critical in early discovery and development of drug candidates through extensive Structure-Activity Relationship (SAR) studies. This chapter contains a primer on the MOA of enzymes and its significance in drug discovery, types of inhibition, development and validation of MOA assays, data analysis and guidelines for performing these assays. New and experienced investigators will find this chapter useful when starting new projects involving enzyme targets.

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References

Literature Cited

    1. Copeland RA. Enzymes: A Practical Introduction to Structure, Mechanism, and Data Analysis, second edition. 2000, Wiley, New York.
    1. Segal IH. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. 1975, Wiley, New York.
    1. Shoichet BK. Screening in a Spirit Haunted World. Drug Discovery Today 2006, v11, pgs 607-615. - PMC - PubMed

Additional References

    1. Copeland RA. Mechanistic Considerations in High-Throughput Screening. Analytical Biochemistry 2003, v320, pgs 1-12. - PubMed
    1. Copeland RA. Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists. 2005, Wiley, New York, - PubMed
    1. Copeland RA, Pompliano DL, Meek TD. Drug-Target Residence Time and Its Implications for Lead Optimization. Nature Reviews Drug Discovery 2006, v5, pgs 730-739. - PubMed
    1. Fehrst A. Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding. 1999, W.H. Freeman, New York.
    1. Kenakin TP. A Pharmacology Primer: Theory, Application, and Methods. 2004, Elsevier, San Diego.

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