Biased signalling: from simple switches to allosteric microprocessors

JS Smith, RJ Lefkowitz, S Rajagopal - Nature reviews Drug discovery, 2018 - nature.com
G protein-coupled receptors (GPCRs) are the largest class of receptors in the human
genome and some of the most common drug targets. It is now well established that GPCRs …

Biased ligands at G-protein-coupled receptors: promise and progress

JD Violin, AL Crombie, DG Soergel, MW Lark - Trends in pharmacological …, 2014 - cell.com
Drug discovery targeting G protein-coupled receptors (GPCRs) is no longer limited to
seeking agonists or antagonists to stimulate or block cellular responses associated with a …

Bias factor and therapeutic window correlate to predict safer opioid analgesics

CL Schmid, NM Kennedy, NC Ross, KM Lovell, Z Yue… - Cell, 2017 - cell.com
Biased agonism has been proposed as a means to separate desirable and adverse drug
responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe …

The role of kinetic context in apparent biased agonism at GPCRs

C Klein Herenbrink, DA Sykes, P Donthamsetti… - Nature …, 2016 - nature.com
Biased agonism describes the ability of ligands to stabilize different conformations of a
GPCR linked to distinct functional outcomes and offers the prospect of designing pathway …

Combinatorial expression of GPCR isoforms affects signalling and drug responses

M Marti-Solano, SE Crilly, D Malinverni, C Munk… - Nature, 2020 - nature.com
G-protein-coupled receptors (GPCRs) are membrane proteins that modulate physiology
across human tissues in response to extracellular signals. GPCR-mediated signalling can …

Biased ligands at opioid receptors: Current status and future directions

T Che, H Dwivedi-Agnihotri, AK Shukla, BL Roth - Science signaling, 2021 - science.org
The opioid crisis represents a major worldwide public health crisis that has accelerated the
search for safer and more effective opioids. Over the past few years, the identification of …

Biased agonism: An emerging paradigm in GPCR drug discovery

Z Rankovic, TF Brust, LM Bohn - Bioorganic & medicinal chemistry letters, 2016 - Elsevier
G protein coupled receptors have historically been one of the most druggable classes of
cellular proteins. The members of this large receptor gene family couple to primary effectors …

Synthesis, chemical characterization, and μ-opioid receptor activity assessment of the emerging group of “nitazene” 2-benzylbenzimidazole synthetic opioids

MM Vandeputte, K Van Uytfanghe… - ACS chemical …, 2021 - ACS Publications
Several 2-benzylbenzimidazole opioids (also referred to as “nitazenes”) recently emerged
on the illicit market. The most frequently encountered member, isotonitazene, has been …

Distinct profiles of functional discrimination among G proteins determine the actions of G protein–coupled receptors

I Masuho, O Ostrovskaya, GM Kramer, CD Jones… - Science …, 2015 - science.org
Members of the heterotrimeric guanine nucleotide–binding protein (G protein)–coupled
receptor (GPCR) family play key roles in many physiological functions and are extensively …

Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential

M Seyedabadi, MH Ghahremani, PR Albert - Pharmacology & therapeutics, 2019 - Elsevier
G protein coupled receptors (GPCRs) convey signals across membranes via interaction with
G proteins. Originally, an individual GPCR was thought to signal through one G protein …