All Outputs (7)

Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor (2014)
Journal Article
Abdul-Ridha, A., Lane, J. R., Mistry, S. N., Lopez, L., Sexton, P. M., Scammells, P. J., …Canals, M. (2014). Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor. Journal of Biological Chemistry, 289(48), 33701-33711. https://doi.org/10.1074/jbc.m114.604967

Benzylquinolone carboxylic acid (BQCA) is the first highly selective positive allosteric modulator (PAM) for the M1 muscarinic acetylcholine receptor (mAChR), but it possesses low affinity for the allosteric site on the receptor. More recent drug dis... Read More about Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor.

A new mechanism of allostery in a G protein-coupled receptor dimer (2014)
Journal Article
Lane, J. R., Donthamsetti, P., Shonberg, J., Draper-Joyce, C. J., Dentry, S., Michino, M., …Christopoulos, A. (2014). A new mechanism of allostery in a G protein-coupled receptor dimer. Nature Chemical Biology, 10(9), 745-752. https://doi.org/10.1038/nchembio.1593

SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identit... Read More about A new mechanism of allostery in a G protein-coupled receptor dimer.

Molecular Mechanisms of Bitopic Ligand Engagement with the M1 Muscarinic Acetylcholine Receptor (2014)
Journal Article
Keov, P., Lopez, L., Devine, S. M., Valant, C., Lane, J. R., Scammells, P. J., …Christopoulos, A. (2014). Molecular Mechanisms of Bitopic Ligand Engagement with the M1 Muscarinic Acetylcholine Receptor. Journal of Biological Chemistry, 289(34), 23817-23837. https://doi.org/10.1074/jbc.M114.582874

TBPB and 77-LH-28-1 are selective agonists of the M1 muscarinic acetylcholine receptor (mAChR) that may gain their selectivity through a bitopic mechanism, interacting concomitantly with the orthosteric site and part of an allosteric site. The curren... Read More about Molecular Mechanisms of Bitopic Ligand Engagement with the M1 Muscarinic Acetylcholine Receptor.

Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D 2Receptor (2014)
Journal Article
Szabo, M., Klein Herenbrink, C., Christopoulos, A., Lane, J. R., & Capuano, B. (2014). Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D 2Receptor. Journal of Medicinal Chemistry, 57(11), 4924-4939. https://doi.org/10.1021/jm500457x

Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D2 receptor (D2R). We investigated the determinants of efficacy, affini... Read More about Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D 2Receptor.

Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D2Receptor (2014)
Journal Article
Szabo, M., Klein Herenbrink, C., Christopoulos, A., Lane, J. R., & Capuano, B. (2014). Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D2Receptor. Journal of Medicinal Chemistry, 57(11), 4924-4939. https://doi.org/10.1021/jm500457x

Biased Agonism at G Protein‐Coupled Receptors: The Promise and the Challenges—A Medicinal Chemistry Perspective (2014)
Journal Article
Shonberg, J., Christopoulos, A., Lopez, L., Scammells, P. J., Capuano, B., & Lane, J. R. (2014). Biased Agonism at G Protein‐Coupled Receptors: The Promise and the Challenges—A Medicinal Chemistry Perspective. Medicinal Research Reviews, 34(6), 1286-1330. https://doi.org/10.1002/med.21318

Historically, determination of G protein?coupled receptor (GPCR) ligand efficacy has often been restricted to identifying the ligand as an agonist or antagonist at a given signaling pathway. This classification was deemed sufficient to predict compou... Read More about Biased Agonism at G Protein‐Coupled Receptors: The Promise and the Challenges—A Medicinal Chemistry Perspective.

Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor (2014)
Journal Article
Abdul-Ridha, A., López, L., Keov, P., Thal, D. M., Mistry, S. N., Sexton, P. M., …Christopoulos, A. (2014). Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor. Journal of Biological Chemistry, 289(9), 6067-6079. https://doi.org/10.1074/jbc.M113.539080

Benzylquinolone carboxylic acid (BQCA) is an unprecedented example of a selective positive allosteric modulator of acetylcholine at the M1 muscarinic acetylcholine receptor (mAChR). To probe the structural basis underlying its selectivity, we utilize... Read More about Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor.