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Composition and applications of focus libraries to phenotypic assays.

Wassermann AM, Camargo LM, Auld DS - Front Pharmacol (2014)

Bottom Line: In this article we discuss the types of compounds in these annotated libraries composed of tools, probes, and drugs.As well, we provide rationale and a few examples for how such libraries can enable phenotypic/forward chemical genomic approaches.As with any approach, there are several pitfalls that need to be considered and we also outline some strategies to avoid these.

View Article: PubMed Central - PubMed

Affiliation: Center for Proteomic Chemistry, Novartis Institutes for Biomedical Research Cambridge, MA, USA.

ABSTRACT
The wealth of bioactivity information now available on low-molecular weight compounds has enabled a paradigm shift in chemical biology and early phase drug discovery efforts. Traditionally chemical libraries have been most commonly employed in screening approaches where a bioassay is used to characterize a chemical library in a random search for active samples. However, robust curating of bioassay data, establishment of ontologies enabling mining of large chemical biology datasets, and a wealth of public chemical biology information has made possible the establishment of highly annotated compound collections. Such annotated chemical libraries can now be used to build a pathway/target hypothesis and have led to a new view where chemical libraries are used to characterize a bioassay. In this article we discuss the types of compounds in these annotated libraries composed of tools, probes, and drugs. As well, we provide rationale and a few examples for how such libraries can enable phenotypic/forward chemical genomic approaches. As with any approach, there are several pitfalls that need to be considered and we also outline some strategies to avoid these.

No MeSH data available.


Related in: MedlinePlus

Small molecules as tools, probes, and drugs. The top bar lists some general features of compounds used as tools, probes, and drugs and example compounds are listed underneath. Color dots designate the primary use of the compounds as a tool (blue), probe (orange), or drug (green). β2-AR, β2-adrenergic receptor; GSH, glutathione S-transferase; CLL, chronic lymphocytic leukemia; ED, erectile dysfunction; PAH, pulmonary arterial hypertension.
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Figure 1: Small molecules as tools, probes, and drugs. The top bar lists some general features of compounds used as tools, probes, and drugs and example compounds are listed underneath. Color dots designate the primary use of the compounds as a tool (blue), probe (orange), or drug (green). β2-AR, β2-adrenergic receptor; GSH, glutathione S-transferase; CLL, chronic lymphocytic leukemia; ED, erectile dysfunction; PAH, pulmonary arterial hypertension.

Mentions: Compounds that have been applied to biological systems can be classified as tools, probes, or drugs (Figure 1). Tool compounds can be broadly applied to understand general biological mechanisms. Examples include cycloheximide (Figure 1), a natural product adopted by cell biologists as a means to study translational mechanisms. Cycloheximide is too toxic for in vivo studies but is widely applied to in vitro cell-based assays. Some compounds such as Actinomycin D (Figure 1), a natural product from bacteria that inhibits the function of RNA polymerase, is both a chemotherapeutic and a tool compound used to test for transcriptional mechanisms. Similarly doxycycline (Figure 1) is used both as an antibacterial drug and as a tool to develop inducible cell-based assays using the tetracycline repressor system (Gossen and Bujard, 1992). The natural product forskolin (Figure 1), and its water-soluble analogs (Laurenza et al., 1987), stimulates adenylate cyclase serving as a critical tool compound to study and develop assays for Gαi/Gαs coupled GPCRs. Such compounds have an essential role in the cell-biologist's tool box.


Composition and applications of focus libraries to phenotypic assays.

Wassermann AM, Camargo LM, Auld DS - Front Pharmacol (2014)

Small molecules as tools, probes, and drugs. The top bar lists some general features of compounds used as tools, probes, and drugs and example compounds are listed underneath. Color dots designate the primary use of the compounds as a tool (blue), probe (orange), or drug (green). β2-AR, β2-adrenergic receptor; GSH, glutathione S-transferase; CLL, chronic lymphocytic leukemia; ED, erectile dysfunction; PAH, pulmonary arterial hypertension.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109565&req=5

Figure 1: Small molecules as tools, probes, and drugs. The top bar lists some general features of compounds used as tools, probes, and drugs and example compounds are listed underneath. Color dots designate the primary use of the compounds as a tool (blue), probe (orange), or drug (green). β2-AR, β2-adrenergic receptor; GSH, glutathione S-transferase; CLL, chronic lymphocytic leukemia; ED, erectile dysfunction; PAH, pulmonary arterial hypertension.
Mentions: Compounds that have been applied to biological systems can be classified as tools, probes, or drugs (Figure 1). Tool compounds can be broadly applied to understand general biological mechanisms. Examples include cycloheximide (Figure 1), a natural product adopted by cell biologists as a means to study translational mechanisms. Cycloheximide is too toxic for in vivo studies but is widely applied to in vitro cell-based assays. Some compounds such as Actinomycin D (Figure 1), a natural product from bacteria that inhibits the function of RNA polymerase, is both a chemotherapeutic and a tool compound used to test for transcriptional mechanisms. Similarly doxycycline (Figure 1) is used both as an antibacterial drug and as a tool to develop inducible cell-based assays using the tetracycline repressor system (Gossen and Bujard, 1992). The natural product forskolin (Figure 1), and its water-soluble analogs (Laurenza et al., 1987), stimulates adenylate cyclase serving as a critical tool compound to study and develop assays for Gαi/Gαs coupled GPCRs. Such compounds have an essential role in the cell-biologist's tool box.

Bottom Line: In this article we discuss the types of compounds in these annotated libraries composed of tools, probes, and drugs.As well, we provide rationale and a few examples for how such libraries can enable phenotypic/forward chemical genomic approaches.As with any approach, there are several pitfalls that need to be considered and we also outline some strategies to avoid these.

View Article: PubMed Central - PubMed

Affiliation: Center for Proteomic Chemistry, Novartis Institutes for Biomedical Research Cambridge, MA, USA.

ABSTRACT
The wealth of bioactivity information now available on low-molecular weight compounds has enabled a paradigm shift in chemical biology and early phase drug discovery efforts. Traditionally chemical libraries have been most commonly employed in screening approaches where a bioassay is used to characterize a chemical library in a random search for active samples. However, robust curating of bioassay data, establishment of ontologies enabling mining of large chemical biology datasets, and a wealth of public chemical biology information has made possible the establishment of highly annotated compound collections. Such annotated chemical libraries can now be used to build a pathway/target hypothesis and have led to a new view where chemical libraries are used to characterize a bioassay. In this article we discuss the types of compounds in these annotated libraries composed of tools, probes, and drugs. As well, we provide rationale and a few examples for how such libraries can enable phenotypic/forward chemical genomic approaches. As with any approach, there are several pitfalls that need to be considered and we also outline some strategies to avoid these.

No MeSH data available.


Related in: MedlinePlus