Chemical probes and drug leads from advances in synthetic planning and methodology

Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article h...

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Published in	Nature reviews. Drug discovery Vol. 17; no. 5; pp. 333 - 352
Main Authors	Gerry, Christopher J., Schreiber, Stuart L.
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.05.2018 Nature Publishing Group
Subjects	631/154/1435 631/154/309 631/92/613 Biomedicine Biotechnology Cancer Research Libraries Medicinal Chemistry Molecular Medicine Pharmacology/Toxicology review-article
Online Access	Get full text
ISSN	1474-1776 1474-1784 1474-1784
DOI	10.1038/nrd.2018.53

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Abstract	Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article highlights how the design and synthesis of such libraries have been enabled by modern synthetic chemistry and illustrates the impact of the resultant chemical probes and drug leads in a wide range of diseases. Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases.
AbstractList	Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from over a decade’s worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases. Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases. Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases.Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases. Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article highlights how the design and synthesis of such libraries have been enabled by modern synthetic chemistry and illustrates the impact of the resultant chemical probes and drug leads in a wide range of diseases.Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases. Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article highlights how the design and synthesis of such libraries have been enabled by modern synthetic chemistry and illustrates the impact of the resultant chemical probes and drug leads in a wide range of diseases. Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases.
Author	Gerry, Christopher J. Schreiber, Stuart L.
AuthorAffiliation	2 The Broad Institute of Harvard & MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA 1 Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA 3 Howard Hughes Medical Institute, Cambridge, Massachusetts 02138, USA
AuthorAffiliation_xml	– name: 2 The Broad Institute of Harvard & MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA – name: 1 Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA – name: 3 Howard Hughes Medical Institute, Cambridge, Massachusetts 02138, USA
Author_xml	– sequence: 1 givenname: Christopher J. surname: Gerry fullname: Gerry, Christopher J. organization: Department of Chemistry and Chemical Biology, Harvard University, The Broad Institute of Harvard & MIT – sequence: 2 givenname: Stuart L. surname: Schreiber fullname: Schreiber, Stuart L. email: schreiber@broadinstitute.org organization: Department of Chemistry and Chemical Biology, Harvard University, The Broad Institute of Harvard & MIT, Howard Hughes Medical Institute
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29651105$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Copyright	Springer Nature Limited 2018 Copyright Nature Publishing Group May 2018
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Snippet	Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with... Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for... Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for...
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Title	Chemical probes and drug leads from advances in synthetic planning and methodology
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