Profiling of compound libraries

In silico ADME profiling of compound libraries in early discovery has become a valuable addition to the research toolbox of computational and medicinal chemists. A computational alert was developed by Lipinski based on the physico-chemical... 

Simenov, A. et al. 2008. Fluorescence spectroscopic profiling of compound libraries. J. Med. Chem. 51, 2363-2371. 

G. Nemeth and D. Kassel, Existing and emerging strategies for the analytical characterization and profiling of compound libraries, in G. Trainor (ed.), Annual Reports in Medicinal Chemistry, Academic Press, 2001, pp. 277-292. 

Simeonov A, Jadhav A, Thomas CJ, Wang Y, Huang R, Southall NT, Shinn P, Smith J, Austin CP, Auld DS, Inglese J. Fluorescence spectroscopic profiling of compound libraries. J. Med. Chem. 2008 51 2363-2371. 

Nemeth, G.A. Kassel, D.B. Existing and Emerging Strategies for the Analytical Characterization and Profiling of Compound Libraries, Annu. Rep. Med. Chem. 36, 277-292 (2001). 

The term chemical assessment describes the process through which the reaction scheme to arrive at a target molecule is combinatorialized. This process may include the transfer of a reaction from solution onto SP and/or the adaptation of the reaction conditions to the use of many monomers with different reactivities and stabilities for library synthesis. Monomer rehearsal is an accurate check of the reactivity of a monomer set in the synthetic scheme for the buildup of the library so that the unreactive/difficult monomers are removed from the set. A model library is a small set of discretes, or a small pool, that is prepared using the planned synthetic route for the library and is fully characterized by the appropriate analytical tools Only if the results are satisfactory is the library synthesis carried out. Quality control determines the analytical profile of a library as a single entity, but data from each library individual, or a significant percentage of library individuals, are acquired. A library with 80% confirmed pure compounds is a good-quality library, but the 20% of samples that are... 

The pharmacophore concept has proven to be extremely successful not only in rationalizing structure-activity relationships, but also by its large impact in developing the appropriate 3D tools for efficient virtual screening. Profiling of combinatorial libraries and compound classification are other often-used applications of this concept. 

Cases M, Garcia-Serna R, Hettne K, Weeber M, van der Lei J, Boyer S, Mestres J. Chemical and biological profiling of an annotated compound library directed to the nuclear receptor family. Curr Top Med Chem 2005 5 763-72. 

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