Christopher Draper-Joyce

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole.

Carmen Klein Herenbrink, Ravi Verma, Herman D Lim, Anitha Kopinathan, Alastair Keen, Jeremy Shonberg, Christopher J Draper-Joyce, Peter J Scammells, Arthur Christopoulos, Jonathan A Javitch, Ben Capuano, Lei Shi, J Robert Lane

Journal article  |  2019  |  ACS Chemical Biology

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the ..

Conformational Transitions and the Activation of Heterotrimeric G Proteins by G Protein-Coupled Receptors.

Christopher Draper-Joyce, Sebastian George Barton Furness

Journal article  |  2019  |  ACS Pharmacology & Translational Science

G protein-coupled receptors (GPCRs) are particularly attractive targets for therapeutic pharmaceuticals. This is because they are ..

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor.

Anitha Kopinathan, Christopher Draper-Joyce, Monika Szabo, Arthur Christopoulos, Peter J Scammells, J Robert Lane, Ben Capuano

Journal article  |  2019  |  Journal of Medicinal Chemistry

SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmac..

Rules of Engagement: GPCRs and G Proteins.

Alisa Glukhova, Christopher J Draper-Joyce, Roger K Sunahara, Arthur Christopoulos, Denise Wootten, Patrick M Sexton

Journal article  |  2018  |  ACS Pharmacology & Translational Science

G protein-coupled receptors (GPCRs) are a key drug target class. They account for over one-third of current pharmaceuticals, and b..

Dominant Negative G Proteins Enhance Formation and Purification of Agonist-GPCR-G Protein Complexes for Structure Determination.

Yi-Lynn Liang, Peishen Zhao, Christopher Draper-Joyce, Jo-Anne Baltos, Alisa Glukhova, Tin T Truong, Lauren T May, Arthur Christopoulos, Denise Wootten, Patrick M Sexton, Sebastian GB Furness

Journal article  |  2018  |  ACS Pharmacology & Translational Science

Advances in structural biology have yielded exponential growth in G protein-coupled receptor (GPCR) structure solution. Nonetheles..

Recent advances in the determination of G protein-coupled receptor structures

David M Thal, Ziva Vuckovic, Christopher J Draper-Joyce, Yi-Lynn Liang, Alisa Glukhova, Arthur Christopoulos, Patrick M Sexton

Journal article  |  2018  |  Current Opinion in Structural Biology

G protein-coupled receptors (GPCRs) are the largest superfamily of cell surface receptor proteins and are important drug targets f..

Structure of the adenosine-bound human adenosine A(1) receptor-G(i) complex

Christopher J Draper-Joyce, Maryam Khoshouei, David M Thal, Yi-Lynn Liang, Anh TN Nguyen, Sebastian GB Furness, Hariprasad Venugopal, Jo-Anne Baltos, Juergen M Plitzko, Radostin Danev, Wolfgang Baumeister, Lauren T May, Denise Wootten, Patrick M Sexton, Alisa Glukhova, Arthur Christopoulos

Journal article  |  2018  |  Nature

The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrime..

Strength in numbers-an arrestin interaction code.

Christopher J Draper-Joyce, Arthur Christopoulos

Journal article  |  2018  |  Nature Structural & Molecular Biology

The structural determinants of the bitopic binding mode of a negative allosteric modulator of the dopamine D2 receptor.

Christopher J Draper-Joyce, Mayako Michino, Ravi Kumar Verma, Carmen Klein Herenbrink, Jeremy Shonberg, Anitha Kopinathan, Peter J Scammells, Ben Capuano, David M Thal, Jonathan A Javitch, Arthur Christopoulos, Lei Shi, J Robert Lane

Journal article  |  2018  |  Biochemical Pharmacology

SB269652 is a negative allosteric modulator of the dopamine D2 receptor (D2R) yet possesses structural similarity to ligands with ..

The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions.

Christopher J Draper-Joyce, Ravi Kumar Verma, Mayako Michino, Jeremy Shonberg, Anitha Kopinathan, Carmen Klein Herenbrink, Peter J Scammells, Ben Capuano, Ara M Abramyan, David M Thal, Jonathan A Javitch, Arthur Christopoulos, Lei Shi, J Robert Lane

Journal article  |  2018  |  Scientific Reports

Sodium ions (Na+) allosterically modulate the binding of orthosteric agonists and antagonists to many class A G protein-coupled re..

Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand.

Shailesh N Mistry, Jeremy Shonberg, Christopher J Draper-Joyce, Carmen Klein Herenbrink, Mayako Michino, Lei Shi, Arthur Christopoulos, Ben Capuano, Peter J Scammells, J Robert Lane

Journal article  |  2015  |  Journal of Medicinal Chemistry

Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxa..

Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor.

Jeremy Shonberg, Christopher Draper-Joyce, Shailesh N Mistry, Arthur Christopoulos, Peter J Scammells, J Robert Lane, Ben Capuano

Journal article  |  2015  |  Journal of Medicinal Chemistry

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to alloste..

A new mechanism of allostery in a G protein-coupled receptor dimer.

J Robert Lane, Prashant Donthamsetti, Jeremy Shonberg, Christopher J Draper-Joyce, Samuel Dentry, Mayako Michino, Lei Shi, Laura López, Peter J Scammells, Ben Capuano, Patrick M Sexton, Jonathan A Javitch, Arthur Christopoulos

Journal article  |  2014  |  Nature Chemical Biology

SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structura..