High through-put screening

In conclusion, it is clear that the S vAr approach to benzofused heterocycles can provide pharmaceutically attractive compounds for high-through-put screening. We anticipate that useful lead molecules will emerge from these studies and look forward to reporting new correlations between bioactivities and molecular structure. 

T. Alefantis, P. Grewal, J. Ashton, A.S. khan, J.J. Valdes and V.G. Del Vecchio, A rapid and sensitive magnetic bead-based immunoassay for the detection of staphylococcal enterotoxin B for high-through put screening, Mol. Cell. Probes, 18 (2004) 379-382. 

J. E. Gonzalez and P. A. Negulescu, Intracellular detection assays for high-through-put screening, Curr. Opin. Biotechnol. 1998, 9, 624- 631. 

Moreover, automation, miniaturization and informatics have facilitated the process known as "high through-put screening," which permits millions of assays per month. 

Numerous modifications are in place at each lab regarding incubation conditions like substrate concentration, incubation time, cofactor use and concentration, protein concentration etc. These modifications depend on the purpose of the method, e.g. as a high through-put screen in early drug discovery or as a tool to characterize a development compound in vitro for regulatory files. Besides these modifications on the biological part of the assay, specific protocols on pipetting robots and conditions used for evaluation by LC-MS/MS also in combination with the instrumental equipment available are applied which are typically not published. Besides LC-MS/MS also LC-UV (Shearer 2002 Stratford 1999) and capillary electrophoresis (Clohs et al. 2002) are described. 

Di et al. (2003) described in detail an automated application on a Packard Multiprobe robot for high through-put screening. The following final concentrations are applied ... 

Madoux, F. et al. 2008. Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-through-put screening. Mol. Pharm. 73, 1776-1784. 

Potyrailo, R. A. Morris, W. G. Wroczynski, R. J., Acoustic-wave sensors for high-through-put screening of materials, In High Throughput Analysis A Tool for Combinatorial Materials Science-, Potyrailo, R. A. Amis, E. J., Eds. Kluwer/Plenum New York, NY, 2003 ch. 11... 

Fig. 14.2 Merging of electrochemistry with the concepts of combinatorial chemistry and high-through-put screening employing miniaturization strategies...

Bleicher KH, Bohm HJ, Muller K, Alanine AL Hit and lead generation beyond high-through-put screening. Nat Rev Drug Discov 2003 2(5) 369 -378. 

Library for repository expansion and high-through-put screening (HTS) (lead finding) Maximum diversity of single library. Maximum diversity within a set of libraries. Find gaps in the represented chemical space. 

Hamid, R., Rotshteyn, Y., Rabadi, L., Parikh, R., and Bullock, P. (2004) Comparison of alamar blue and MTT assays for high through-put screening. Toxicol, in Vitro,... 

Henning Vollert, Birgit Jordan and hvin Winkler, Wandel in der Wirkstoffsuche -Ultra-High-Through-put-Screening-Systeme in der Pharmaindustrie, lABORWELT, 1 (2000), 5-10. 

It is hoped that concerted efforts with computational chemistry, focused combinatorial chemistry, high-through-put screening, and SAR by NMR and X-ray will accelerate the rational translation of functional epitopes displayed by protein tertiary structures on to a small molecular scaffold and make this approach more feasible in the near future.2 ... 

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