A ligand's view of target similarity: chemogenomic binding site-directed techniques for drug discovery

Research output: Contribution to journalJournal articlepeer-review

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A ligand's view of target similarity : chemogenomic binding site-directed techniques for drug discovery. / Garland, Stephen L; Gloriam, David E.

In: Current Topics in Medicinal Chemistry, Vol. 11, No. 15, 2011, p. 1872-1881.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Garland, SL & Gloriam, DE 2011, 'A ligand's view of target similarity: chemogenomic binding site-directed techniques for drug discovery', Current Topics in Medicinal Chemistry, vol. 11, no. 15, pp. 1872-1881.

APA

Garland, S. L., & Gloriam, D. E. (2011). A ligand's view of target similarity: chemogenomic binding site-directed techniques for drug discovery. Current Topics in Medicinal Chemistry, 11(15), 1872-1881.

Vancouver

Garland SL, Gloriam DE. A ligand's view of target similarity: chemogenomic binding site-directed techniques for drug discovery. Current Topics in Medicinal Chemistry. 2011;11(15):1872-1881.

Author

Garland, Stephen L ; Gloriam, David E. / A ligand's view of target similarity : chemogenomic binding site-directed techniques for drug discovery. In: Current Topics in Medicinal Chemistry. 2011 ; Vol. 11, No. 15. pp. 1872-1881.

Bibtex

@article{e834d03a04084575a8a5fb1114dd1239,
title = "A ligand's view of target similarity: chemogenomic binding site-directed techniques for drug discovery",
abstract = "GPCR binding site-directed techniques are rapidly evolving into powerful tools for modern drug discovery. Many of these approaches bridge chemistry and biology, which are inseparable concepts in nature but are often treated as separate worlds in drug discovery and science in general. This review shows with several examples how focusing on the binding site(s) has a clear advantage when it comes to establishing sequence-correlated pharmacological profiles. By organizing and comparing sequence and structural data it is possible to {"}borrow{"} SAR from similar targets to increase the speed of lead-finding and, potentially, to produce ligands for previously intractable receptors. Sequence motifs correlated with ligands can be applied in the design of target-specific focused libraries that are both efficient and cost-effective and should provide increased hit-rates over diversity screening. Furthermore, in the optimization phase, the binding motif approach offers the possibility to identify quickly the most likely off-target candidates to be chosen for selectivity screening, as well as potentially characterizing those pockets which may best be exploited for improved selectivity.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Garland, {Stephen L} and Gloriam, {David E}",
note = "Keywords: chemogenomics; GPCR; 7TM; lead generation; selectivity; polypharmacology; Privileged structures; compound library design",
year = "2011",
language = "English",
volume = "11",
pages = "1872--1881",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers",
number = "15",

}

RIS

TY - JOUR

T1 - A ligand's view of target similarity

T2 - chemogenomic binding site-directed techniques for drug discovery

AU - Garland, Stephen L

AU - Gloriam, David E

N1 - Keywords: chemogenomics; GPCR; 7TM; lead generation; selectivity; polypharmacology; Privileged structures; compound library design

PY - 2011

Y1 - 2011

N2 - GPCR binding site-directed techniques are rapidly evolving into powerful tools for modern drug discovery. Many of these approaches bridge chemistry and biology, which are inseparable concepts in nature but are often treated as separate worlds in drug discovery and science in general. This review shows with several examples how focusing on the binding site(s) has a clear advantage when it comes to establishing sequence-correlated pharmacological profiles. By organizing and comparing sequence and structural data it is possible to "borrow" SAR from similar targets to increase the speed of lead-finding and, potentially, to produce ligands for previously intractable receptors. Sequence motifs correlated with ligands can be applied in the design of target-specific focused libraries that are both efficient and cost-effective and should provide increased hit-rates over diversity screening. Furthermore, in the optimization phase, the binding motif approach offers the possibility to identify quickly the most likely off-target candidates to be chosen for selectivity screening, as well as potentially characterizing those pockets which may best be exploited for improved selectivity.

AB - GPCR binding site-directed techniques are rapidly evolving into powerful tools for modern drug discovery. Many of these approaches bridge chemistry and biology, which are inseparable concepts in nature but are often treated as separate worlds in drug discovery and science in general. This review shows with several examples how focusing on the binding site(s) has a clear advantage when it comes to establishing sequence-correlated pharmacological profiles. By organizing and comparing sequence and structural data it is possible to "borrow" SAR from similar targets to increase the speed of lead-finding and, potentially, to produce ligands for previously intractable receptors. Sequence motifs correlated with ligands can be applied in the design of target-specific focused libraries that are both efficient and cost-effective and should provide increased hit-rates over diversity screening. Furthermore, in the optimization phase, the binding motif approach offers the possibility to identify quickly the most likely off-target candidates to be chosen for selectivity screening, as well as potentially characterizing those pockets which may best be exploited for improved selectivity.

KW - Former Faculty of Pharmaceutical Sciences

M3 - Journal article

C2 - 21470171

VL - 11

SP - 1872

EP - 1881

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 15

ER -

ID: 35921541