Screening retrospective

Bagdy D., Barabas E., Bajusz S., Szell E. In vitro inhibition of blood coagulation by tripeptide aldehydes A retrospective screening study focused on the stable D-MePhe-Pro-Atg-H-H2S04. Thromb Haemost 1992 67,325-30. 

Fig. 3.3 Elements of the Euler-Venn diagrams represent compounds that were found among the first 5% of the similarity-ranked list that results from retrospective screening with the (a) COX2, (b) HIV protease and (c) MMP datasets of the COBRA dataset. The Manhattan distance...

In a subsequent study, we examined the influence of seven similarity indices on the enrichment of actives using the topological CATS descriptor and the 12 COBRA datasets [31]. In particular, we evaluated to what extent different similarity measures complement each other in terms of the retrieved active compounds. Retrospective screening experiments were carried out with seven similarity measures Manhattan distance, Euclidian distance, Tanimoto coefficient, Soergel distance, Dice coefficient, cosine coefficient, and spherical distance. Apart from the GPCR dataset, considerable enrichments were achieved. Enrichment factors for the same datasets but different similarity measures differed only slightly. For most of the datasets the Manhattan and the Soergel distance... 

Retrospective screening was performed in the same manner as by Fechner et al. [33], leaving out the two very general classes GPCR and nuclear receptors. The average enrichment factors for the first 5% of the database are shown in Fig. 3.5. 

Fig. 3.12 Comparison of the enrichment curves of the SQUID COX-2 model with CATS3D retrospective screening with the molecules used for pharmacophore model calculation.

Figure 13.6 Results of retrospective screening with CVR methods.

Figure 13.8 Comparison of the enrichment obtained with the combined pharmacophore model (PPP model) resulting from a 1,5-A PPP cluster radius with the results of retrospective screening using the COX-2 inhibitors Rofecoxib, M5, and SC-558 as seed structures (courtesy S. Renner).

An example of a transformation of a peptide inhibitor structure into a small molecule is the retrospective screening for thrombin inhibitors. The 3-D structure of thrombin with the bound D-Phe-Pro-Arg peptide is shown in Fig. 4.5. 

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