Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

Structure-activity relationship analysis on the basis of matched molecular pairs

Journal of Cheminformatics20146(Suppl 1):O14

DOI: 10.1186/1758-2946-6-S1-O14

Published: 11 March 2014

Matched molecular pairs (MMPs), i.e., pairs of compounds that are related to each other by a specific molecular transformation, have become an integral tool of drug discovery [1, 2]. Generally spoken, matched molecular pair analysis (MMPA) aims at the extraction of all MMPs from a set of compounds and their association with calculated or measured property changes. Using public bioactivity data, we have used MMPs as a consistent reference framework to identify sets of chemical replacements that either have the propensity to induce large-magnitude potency changes or tend to retain compound potency across diverse targets [3, 4]. Furthermore, we have extended the concept of MMPs to matched molecular series, i.e., analog series with different molecular core structures but corresponding substitution patterns [5, 6]. The identification of series with alternative core structures but similar SAR trends is highly relevant for lead optimization where SAR information from one series that has been explored historically is ideally used to guide compound design efforts for a new chemotype [6].

Authors’ Affiliations

(1)
Novartis Institutes for Biomedical Research

References

  1. Griffen E, Leach AG, Robb GR, Warner DJ: Matched molecular pairs as a medicinal chemistry tool. J Med Chem. 2011, 54: 7739-7750. 10.1021/jm200452d.View ArticleGoogle Scholar
  2. Dossetter AG, Griffen EJ, Leach AG: Matched molecular pair analysis in drug discovery. Drug Discov Today. 2013, 18: 724-731. 10.1016/j.drudis.2013.03.003.View ArticleGoogle Scholar
  3. Wassermann AM, Bajorath J: Chemical substitutions that introduce activity cliffs across different compound classes and biological targets. J Chem Inf Model. 2010, 50: 1248-1256. 10.1021/ci1001845.View ArticleGoogle Scholar
  4. Wassermann AM, Bajorath J: Large-scale exploration of bioisosteric replacements on the basis of matched molecular pairs. Future Med Chem. 2011, 3: 425-436. 10.4155/fmc.10.293.View ArticleGoogle Scholar
  5. Wawer M, Bajorath J: Local structural changes, global data views: graphical substructure-activity relationship trailing. J Med Chem. 2011, 54: 2944-2951. 10.1021/jm200026b.View ArticleGoogle Scholar
  6. Wassermann AM, Bajorath J: A data mining method to facilitate SAR transfer. J Chem Inf Model. 2011, 51: 1857-1866. 10.1021/ci200254k.View ArticleGoogle Scholar

Copyright

© Wassermann; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.