Limits...
The 'SAR Matrix' method and its extensions for applications in medicinal chemistry and chemogenomics.

Gupta-Ostermann D, Bajorath J - F1000Res (2014)

Bottom Line: The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets.It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces.The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universit├Ąt, Bonn, D-53113, Germany.

ABSTRACT
We describe the 'Structure-Activity Relationship (SAR) Matrix' (SARM) methodology that is based upon a special two-step application of the matched molecular pair (MMP) formalism. The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets. It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces. The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

No MeSH data available.


SAR patterns in matrices.In (a), a SARM capturing 16 ligands of the histamine H4 receptor is shown. Cells containing analogs with preferred cores yielding potent compounds are framed in blue. Substructures distinguishing the core fragments are highlighted in red. The pKi value range for the 16 ligands is displayed. In (b), a subset of a double-cut SARM is shown that contains series of carbonic anhydrase I inhibitors and an exemplary SAR transfer event.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4215758&req=5

f2: SAR patterns in matrices.In (a), a SARM capturing 16 ligands of the histamine H4 receptor is shown. Cells containing analogs with preferred cores yielding potent compounds are framed in blue. Substructures distinguishing the core fragments are highlighted in red. The pKi value range for the 16 ligands is displayed. In (b), a subset of a double-cut SARM is shown that contains series of carbonic anhydrase I inhibitors and an exemplary SAR transfer event.

Mentions: In SARMs, different types of SAR patterns become readily apparent. This is illustrated inFigure 2 that shows exemplary SARMs revealing characteristic patterns (for representation purposes, only small matrices are shown;vide infra). For example, the SARM inFigure 2a identifies two preferred core structures that consistently produce potent compounds. Furthermore, the SARM inFigure 2b reveals an SAR transfer event, i.e., the presence of two compound series with related yet distinct core structures that contain pairwise corresponding analogs with similar potency progression. Other SAR patterns that can frequently be detected include, for example, preferred R-groups (or R-group combinations) in related compound series or regions of distinct SAR continuity or discontinuity. Continuous SAR regions are characterized by the presence of compounds with structural modifications that lead to gradual changes in potency, whereas discontinuous SAR regions contain structural analogs with large (and essentially unpredictable) potency variations2.


The 'SAR Matrix' method and its extensions for applications in medicinal chemistry and chemogenomics.

Gupta-Ostermann D, Bajorath J - F1000Res (2014)

SAR patterns in matrices.In (a), a SARM capturing 16 ligands of the histamine H4 receptor is shown. Cells containing analogs with preferred cores yielding potent compounds are framed in blue. Substructures distinguishing the core fragments are highlighted in red. The pKi value range for the 16 ligands is displayed. In (b), a subset of a double-cut SARM is shown that contains series of carbonic anhydrase I inhibitors and an exemplary SAR transfer event.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4215758&req=5

f2: SAR patterns in matrices.In (a), a SARM capturing 16 ligands of the histamine H4 receptor is shown. Cells containing analogs with preferred cores yielding potent compounds are framed in blue. Substructures distinguishing the core fragments are highlighted in red. The pKi value range for the 16 ligands is displayed. In (b), a subset of a double-cut SARM is shown that contains series of carbonic anhydrase I inhibitors and an exemplary SAR transfer event.
Mentions: In SARMs, different types of SAR patterns become readily apparent. This is illustrated inFigure 2 that shows exemplary SARMs revealing characteristic patterns (for representation purposes, only small matrices are shown;vide infra). For example, the SARM inFigure 2a identifies two preferred core structures that consistently produce potent compounds. Furthermore, the SARM inFigure 2b reveals an SAR transfer event, i.e., the presence of two compound series with related yet distinct core structures that contain pairwise corresponding analogs with similar potency progression. Other SAR patterns that can frequently be detected include, for example, preferred R-groups (or R-group combinations) in related compound series or regions of distinct SAR continuity or discontinuity. Continuous SAR regions are characterized by the presence of compounds with structural modifications that lead to gradual changes in potency, whereas discontinuous SAR regions contain structural analogs with large (and essentially unpredictable) potency variations2.

Bottom Line: The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets.It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces.The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universit├Ąt, Bonn, D-53113, Germany.

ABSTRACT
We describe the 'Structure-Activity Relationship (SAR) Matrix' (SARM) methodology that is based upon a special two-step application of the matched molecular pair (MMP) formalism. The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets. It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces. The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

No MeSH data available.