Journal: Molecular Systems Biology

Article Title: Analysis of multiple compound–protein interactions reveals novel bioactive molecules

doi: 10.1038/msb.2011.5

Figure Lengend Snippet: Compound IDs and names (see Supplementary Table S4 for the chemical structures)

Article Snippet: To assess this ability, we analyzed 11 500 compounds from the Bionet chemical library (Key Organics Ltd, Cornwall, UK) to predict compounds likely to bind to two GPCRs from different subfamilies, ADRB2 and NPY1R ( ).

Techniques:

Journal: Molecular Systems Biology

Article Title: Analysis of multiple compound–protein interactions reveals novel bioactive molecules

doi: 10.1038/msb.2011.5

Figure Lengend Snippet: Experimental confirmation of in vitro GPCR activity of compounds and their scaffolds screened from a chemical library. Dose–response curves of the top-ranked compounds from the Bionet chemical library for ( A ) ADRB2 agonists, ( B ) ADRB2 antagonists, and ( C ) NPY1R agonists. Inactive compounds (cutoff of 100 μM in EC 50 /IC 50 value) are not shown. Red lines indicate results for compounds exhibiting scaffold hopping based on the criteria explained in the Results section. Blue lines indicate results from compounds with almost completely overlapping structures. Compounds 29 ( N -( tert -butyl)- N ′-(4-methoxybenzyl)thiourea), 30 (2-ethyl-2-{[(2-fluorobenzyl)oxy]methyl}-5,5-dimethyltetrahydrofuran), and 5 are corresponding to the curves in A from left to right. Compounds 8 , 33 , 30 , 28 (2-[2,5-dimethyl-4-(morpholinomethyl)phenoxy]acetamide), 31 (2-(3-isopropoxyphenyl)-1-ethanamine), 9 ((2-aminophenyl)(4-methylphenyl)amine), and 32 (2-morpholino-2-oxoacetohydrazide) are corresponding to the curves in B from left to right. Compounds 12 , 34 , and 15 (diethyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-hydroxy-3,5-pyridinedicarboxylate) are corresponding to the curves in C from left to right. ( D ) Max-MCSs between identified active compounds (left) and the most relevant compounds found within the entire training compound data set (center) or within the ligand set of each target protein (right) that exhibited scaffold hopping. The max-MCSs between compounds are indicated in red. The columns ‘bioactivity' and ‘ligand' indicate the existence of publications regarding the active compound: ‘bioactivity' indicates whether a publication has already described that the compound is bioactive; ‘ligand' indicates whether a publication has uncovered the ADBR2/NPY1R ligand activity, having known the compound is bioactive. All identified active compounds are shown in Supplementary Figure S9. See Table I for compound names of the numbered compounds.

Article Snippet: To assess this ability, we analyzed 11 500 compounds from the Bionet chemical library (Key Organics Ltd, Cornwall, UK) to predict compounds likely to bind to two GPCRs from different subfamilies, ADRB2 and NPY1R ( ).

Techniques: In Vitro, Activity Assay

Journal: Molecular Systems Biology

Article Title: Analysis of multiple compound–protein interactions reveals novel bioactive molecules

doi: 10.1038/msb.2011.5

Figure Lengend Snippet: Experimental confirmation of the in vitro kinase activity of compounds and their scaffolds screened from a chemical library. Dose–response curves of the top-ranked compounds from the Bionet chemical library for EGFR tyrosine kinase inhibitor activity ( A ) and CDK2 inhibitor activity ( B ). Inactive compounds (cutoff of 100 μM in IC 50 value) are not shown. Color of lines in A and B is the same as in . Compounds 18 , 36 , 21 , 35 , and 37 are corresponding to the curves in A from left to right. Compounds 26 ([4-amino-2-( tert -butylamino)-1,3-thiazol-5-yl](4-chlorophenyl)methanone) and 23 are corresponding to the curves in B from left to right. ( C ) Max-MCSs and publication status are similar to for the EGFR and CDK2. See for compound names of the numbered compounds.

Article Snippet: To assess this ability, we analyzed 11 500 compounds from the Bionet chemical library (Key Organics Ltd, Cornwall, UK) to predict compounds likely to bind to two GPCRs from different subfamilies, ADRB2 and NPY1R ( ).

Techniques: In Vitro, Activity Assay