SPECS compound library

Figure 11.4 Self-organizing map used for screening the SPECS compound library.

Figure 7.9 New hits for inhibitors of P-glycoprotein identified in an in silico screening of the SPECS compound library using a selforganizing map.

Specs, founded in 1987 and based in Delft, The Netherlands, purchases compounds from all over the world, mostly from academic laboratories. These compounds are added to Specs existing library and in turn sold to interested companies. A company can search the Specs library and purchase promising compounds or the entire collection. Those compounds become the outright property of the purchasing company. If Specs has a sufficient amount of a given compound, the company will sell samples of each compound many times over. The amount sold for each compound may be only 0.5 to 1.0 mg. 

If the network indeed places highly active compounds in close vicinity vdth each other, compounds from the SPECS library colocalizing with highly active propafenone derivatives should also be active. Finally, seven compounds with completely different chemical scaffolds were retrieved and pharmacologically tested [32]. Two out of them showed inhibitory activity with IC50 values in the submicromolar range, which definitely renders them new lead compounds for P-gp (Figure 7.9). 

Parallel to the synthesis of library compounds on solid supports, the direct analysis (i.e. on-bead ) is an attractive concept. Leaving aside the methods of on-bead-infrared-spec-troscopy [41] using attenuated total reflection (ATR) and gel-phase NMR-techniques [42, 43], we wish to consider the use of on-bead analysis in mass spectrometry. The requirements of the ionization process restrict on-bead analysis to the MALD1 technique. However, also for MALDI-analysis, in so-called direct monitoring studies [44-46], the compounds are cleaved from the bead before the actual ionization. True on-bead analysis under MALDI conditions is only possible with photolytically cleavable linkers, and this technique has been dealt with in several publications [28,29] in which the compounds are both cleaved and ionized simultaneously within the MALDI source with a single laser shot. The wavelength of the MALDI-laser must however correspond with the wavelength required to cleave the compounds from the resin. Therefore, on-bead analysis represents a method for special analytical problems which is limited to MALDI. 

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