{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:32:09Z","timestamp":1787045529075,"version":"build-2736575974"},"reference-count":18,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To solve recurring problems in drug discovery, matched molecular pair (MMP) analysis is used to understand relationships between chemical structure and function. For the MMP analysis of large data sets (&amp;gt;10,000 compounds), available tools lack flexible search and visualization functionality and require computational expertise. Here, we present Matcher, an open-source application for MMP analysis, with novel search algorithms and fully automated querying-to-visualization that requires no programming expertise. Matcher enables unprecedented control over the search and clustering of MMP transformations based on both variable fragment and constant environment structure, which is critical for disentangling relevant and irrelevant data to a given problem. Users can exert such control through a built-in chemical sketcher and with a few mouse clicks can navigate between resulting MMP transformations, statistics, property distribution graphs, and structures with raw experimental data, for confident and accelerated decision making. Matcher can be used with any collection of structure\/property data; here, we demonstrate usage with a public ChEMBL data set of about 20,000 small molecules with CYP3A4 and\/or hERG inhibition data. Users can reproduce all examples demonstrated herein via unique links within Matcher\u2019s interface\u2013a functionality that anyone can use to preserve and share their own analyses. Matcher and all its dependencies are open-source, can be used for free, and are available with containerized deployment from code at https:\/\/github.com\/Merck\/Matcher. Matcher makes large structure\/property data sets more transparent than ever before and accelerates the data-driven solution of common problems in drug discovery.<\/jats:p>","DOI":"10.1021\/acs.jcim.3c00015","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T16:17:15Z","timestamp":1680020235000},"page":"1852-1857","source":"Crossref","is-referenced-by-count":3,"title":["Matcher: An Open-Source\nApplication for Translating\nLarge Structure\/Property Data Sets into Insights for Drug Design"],"prefix":"10.1021","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-4965","authenticated-orcid":true,"given":"Andrew J.","family":"Hoover","sequence":"first","affiliation":[{"name":"Merck & Co., Inc. , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4180-270X","authenticated-orcid":true,"given":"Martin","family":"Spale","sequence":"additional","affiliation":[{"name":"R&D Informatics Solutions, MSD Czech Republic s.r.o. , ,","place":["Prague, Czech Republic, 150 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-3603","authenticated-orcid":true,"given":"Brian","family":"Lahue","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3282-1017","authenticated-orcid":true,"given":"Danny A.","family":"Bitton","sequence":"additional","affiliation":[{"name":"R&D Informatics Solutions, MSD Czech Republic s.r.o. , ,","place":["Prague, Czech Republic, 150 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"2026081804440079000_cit1","doi-asserted-by":"publisher","first-page":"7739","DOI":"10.1021\/jm200452d","article-title":"Matched Molecular\nPairs as a Medicinal Chemistry Tool","volume":"54","author":"Griffen","year":"2011","journal-title":"J. Med.\nChem."},{"key":"2026081804440079000_cit2","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/ddr.21045","article-title":"Advances in Computational\nMedicinal Chemistry: Matched Molecular Pair Analysis","volume":"73","author":"Wassermann","year":"2012","journal-title":"Drug Dev. Res."},{"key":"2026081804440079000_cit3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.csbj.2016.12.003","article-title":"Matched Molecular Pair Analysis in Short: Algorithms,\nApplications and Limitations. Comput","volume":"15","author":"Tyrchan","year":"2017","journal-title":"Struct.\nBiotechnol. J."},{"key":"2026081804440079000_cit4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1021\/ci0503208","article-title":"Molecular\nTransformations as a Way\nof Finding and Exploiting Consistent Local QSAR","volume":"46","author":"Sheridan","year":"2006","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804440079000_cit5","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1021\/ci900450m","article-title":"Computationally Efficient Algorithm to Identify Matched Molecular\nPairs (MMPs) in Large Data Sets","volume":"50","author":"Hussain","year":"2010","journal-title":"J. Chem. Inf.\nModel."},{"key":"2026081804440079000_cit6","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.1016\/j.bmc.2011.05.003","article-title":"Extraction\nof Tacit Knowledge from\nLarge ADME Data Sets via Pairwise Analysis","volume":"19","author":"Keefer","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"2026081804440079000_cit7","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1021\/ci100084s","article-title":"WizePairZ:\nA Novel Algorithm to Identify,\nEncode, and Exploit Matched Molecular Pairs with Unspecified Cores\nin Medicinal Chemistry","volume":"50","author":"Warner","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804440079000_cit8","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1021\/acs.jcim.7b00335","article-title":"Turbocharging\nMatched Molecular Pair Analysis: Optimizing the Identification and\nAnalysis of Pairs","volume":"57","author":"Lukac","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804440079000_cit9","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1021\/acs.jcim.8b00173","article-title":"mmpdb: An\nOpen-Source Matched Molecular\nPair Platform for Large Multiproperty Data Sets","volume":"58","author":"Dalke","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804440079000_cit10","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1021\/acs.jcim.0c00583","article-title":"The Derivation\nof a Matched Molecular Pairs Based ADME\/Tox Knowledge Base for Compound\nOptimization","volume":"60","author":"Lumley","year":"2020","journal-title":"J. Chem. Inf. 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