Abstract
Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.
| Original language | English |
|---|---|
| Pages (from-to) | 551-556 |
| Number of pages | 6 |
| Journal | Current Opinion in Pharmacology |
| Volume | 3 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2003 |
| Externally published | Yes |
Cite this
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Allosteric modulators of G-protein-coupled receptors. / May, Lauren T.; Christopoulos, Arthur.
In: Current Opinion in Pharmacology, Vol. 3, No. 5, 10.2003, p. 551-556.Research output: Contribution to journal › Review Article › Research › peer-review
TY - JOUR
T1 - Allosteric modulators of G-protein-coupled receptors
AU - May, Lauren T.
AU - Christopoulos, Arthur
PY - 2003/10
Y1 - 2003/10
N2 - Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.
AB - Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.
UR - http://www.scopus.com/inward/record.url?scp=0141869933&partnerID=8YFLogxK
U2 - 10.1016/S1471-4892(03)00107-3
DO - 10.1016/S1471-4892(03)00107-3
M3 - Review Article
VL - 3
SP - 551
EP - 556
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
SN - 1471-4892
IS - 5
ER -