Table 2 Experimentally validated β2R hits based on the IFP, PLANTS and combined approach.

From: Function-specific virtual screening for GPCR ligands using a combined scoring method

  1. aThe letters C, I and P, refer to the distinct compound selections from each the Combined, IFP and PLANTS scoring approach, respectively. Combinations like C + I indicate that the compound was present in both the selection of the Combined and the IFP scoring approach but not the PLANTS approach. Further details are shown in Fig. 3. REF indicates reference compounds. bpEC50 values are calculated from at least three independent measurements as the mean ± SEM. cMaximum CRE-luciferase response values normalized to isoproterenol (100%) and basal activity (0%) using HEK293T cells transiently expressing the human β2R. For values preceded by “>” the maximum response plateau was not observed, therefore the response at 100 μM was reported (except for compounds 50, 53, 59, 65 and 71, for which the response at 10μM is reported). dIFP Tanimoto similarity to the pose of BI-167107 in the β2R crystal structure. Optimized IFP score cut-off ≥0.75. IFP ranking is given between brackets. eScore and rank according to PLANTS scoring function19. Optimized PLANTS score cut-off ≤−90. PLANTS ranking is given between brackets. fROCS shape-based 3D similarity to BI-167107 based on Comboscore69. ROCS ranking is given between brackets. gECFP-4 2D Tanimoto similarity to BI-167107. A similarity higher than 0.40 is considered as significative21. ECFP-4 ranking is given between brackets. hECFP-4 circular fingerprint Tanimoto similarity to closest known β2R active in ChEMBLdb. A similarity higher than 0.40 is considered as significative21. iThe closest known β2R active in the ChEMBLdb as determined by the ECFP-4 similarity. jThe rankings indicated for reference BI-167107 and isoprenaline were determined as if they were included in the screening library.