Constellation Pharmacology: A New Paradigm for Drug Discovery

• Published in: Annual review of pharmacology and toxicology Vol. 55; no. 1; pp. 573 - 589
• Main Authors: Teichert, Russell W, Schmidt, Eric W, Olivera, Baldomero M
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 01-01-2015
• Subjects: Animals; conotoxin; constellation pharmacology; dorsal root ganglia; Drug Discovery - methods; high-content screen; High-Throughput Screening Assays - methods; Humans; Molecular Targeted Therapy; Neural Pathways - drug effects; Neural Pathways - metabolism; Neurons - classification; Neurons - drug effects; Neurons - metabolism; Peptides - isolation & purification; Peptides - pharmacology; Pharmacology - methods; Signal Transduction - drug effects; somatosensory neuron; Venoms - chemistry; Venoms - pharmacology; conotoxin; high-content screen; constellation pharmacology; dorsal root ganglia; somatosensory neuron
• ISSN: 0362-1642; 1545-4304
• DOI: 10.1146/annurev-pharmtox-010814-124551

Constellation pharmacology is a cell-based high-content phenotypic-screening platform that utilizes subtype-selective pharmacological agents to elucidate the cell-specific combinations (constellations) of key signaling proteins that define specific cell types. Heterogeneous populations of native cells, in which the different individual cell types have been identified and characterized, are the foundation for this screening platform. Constellation pharmacology is useful for screening small molecules or for deconvoluting complex mixtures of biologically active natural products. This platform has been used to purify natural products and discover their molecular mechanisms. In the ongoing development of constellation pharmacology, there is a positive feedback loop between the pharmacological characterization of cell types and screening for new drug candidates. As constellation pharmacology is used to discover compounds with novel targeting-selectivity profiles, those new compounds then further help to elucidate the constellations of specific cell types, thereby increasing the content of this high-content platform.