This paper describes an original approach for extracting outstanding pharmacophores, named PADs (... more This paper describes an original approach for extracting outstanding pharmacophores, named PADs (for Pharmacophore Activity Delta), from a chemogenomic dataset (BCR-ABL in our case). This involves building both a partial order graph (POG) and a condensed POG as a first step to finally land on PADs to be assessed. A pharmacophore is a PAD if its quality deviates at least δ standard deviations from the mean of the quality (growth rate value) of its siblings. From 1479 molecules, 377 PADs were extracted. PADs were summarized afterwards by 130 representative PADs with the MMRFS technique. To analyze these PADs, a pharmacophore network was derived, leading to different areas associated with active and inactive molecules. A discussion of some representative key areas is carried out, pointing out some structure–activity relationships (SARs). Cross-validation studies were also carried out with a potential selection of the most stable PADs for SARs.
This paper describes an original approach for extracting outstanding pharmacophores, named PADs (... more This paper describes an original approach for extracting outstanding pharmacophores, named PADs (for Pharmacophore Activity Delta), from a chemogenomic dataset (BCR-ABL in our case). This involves building both a partial order graph (POG) and a condensed POG as a first step to finally land on PADs to be assessed. A pharmacophore is a PAD if its quality deviates at least δ standard deviations from the mean of the quality (growth rate value) of its siblings. From 1479 molecules, 377 PADs were extracted. PADs were summarized afterwards by 130 representative PADs with the MMRFS technique. To analyze these PADs, a pharmacophore network was derived, leading to different areas associated with active and inactive molecules. A discussion of some representative key areas is carried out, pointing out some structure–activity relationships (SARs). Cross-validation studies were also carried out with a potential selection of the most stable PADs for SARs.
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Papers by Etienne LEHEMBRE