Multitarget screening

Jenwitheesuk, E., Horst, J.A., Rivas, KL., Van Voorhis, W.C. and Samudrala, R. (2008) Novel paradigms for drug discovery computational multitarget screening. Trends in Pharmacological Sciences, 29, 62-71. 

J Trias, Z Yuan. Mining bacterial cell wall biosynthesis with new tools multitarget screens. Drug Res Updates 2 358-362, 1999. 

Mueller CA, Weinmann W, Dresen S, Schreiber A, Gergov M. Development of a multitarget screening analysis for 301 drugs using a QTrap liquid chromatography/tandem mass spectrometry system and automated library searching. Rapid Commun Mass Spectrom 2005 19 1332-1338. 

Several affinity screening methodologies that include MS-based readout and work under protein-excess conditions have been developed in the past decade [1]. Some examples include affinity selection/mass spectrometry (ASMS Abbott Labs [10]), size exclusion chromatography with LC-ESI-MS (see Chapter 2 and 3 [11-19]), the use of coupled or non-coupled pulsed ultra-filtration/mass spectrometry (summarized in this chapter [11, 20-23]), restricted access phase chromatography (see Chapter 5 [24, 25]), capillary electrophoresis [26, 27], target shift mass spectrometry [28], and multitarget affinity/specificity screening (MASS, see Chapter 10 [29, 30]). 

Multitarget Affinity/Specificity Screening in a High Throughput Format... 

Fig. 10.6 Concept of multitarget affinity specificity screening (MASS). Macromolecular targets (typically structured RNA constructs or proteins) in nondenaturing buffers are mixed in solution with a collection of potential ligands derived from natural product fractions, combinatorial libraries, or other diverse compound collections. The...

We have developed a mass spectrometry-based approach for discovery of small-molecule drugs that work by binding to structured regions of ribonucleic acids (RNA). This approach is called Multitarget Affinity/Specificity Screening... 

R.H. Hofstadler, S.A. Multitarget Affinity/Specificity Screening of Natural Prod-... 

Bender, A., Jenkins, J. L., Click, M., et al. 2006. "Bayes affinity fingerprints" improve retrieval rates in virtual screening and define orthogonal bioactivity space When are multitarget drugs a feasible concept /. Chem. Inf. Model. 46 2445-2456. 

SAS maps have also been used to represent consensus models of activity landscapes by means of fusing similarity measures obtained from different 2D and 3D molecule representations and similarity functions [145,189,191]. In addition, SAS maps were recently adapted to model multitarget activity landscapes by representing in one axis the activity similarity of compound datasets screened across multiple biological endpoints [192]. SAS maps have been extended to characterize property landscapes other than activity landscapes. For example, stmcture-flavor similarity maps have been proposed to systematically characterize stmcture-flavor associations of a comprehensive flavor database [182]. A number of additional types of 2D MFS maps that characterize a different fusion-based similarity on each axis have also been developed and are described in Section 15.5.3. 

---