Related Experiment Video
Updated: Jan 11, 2026

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
Published on: March 10, 2020
A New Era for PPARγ: Covalent Ligands and Therapeutic Applications
Jasmine L King1, Luke Smithers1, Alice Vrielink1
1School of Molecular Sciences, The University of Western Australia, Crawley, 6009 Perth, Australia.
None:
Peroxisome proliferator-activated receptor γ (PPARγ) is a prominent ligand-inducible transcription factor involved in adipocyte differentiation, glucose homeostasis, insulin sensitivity, inflammation, and cell proliferation, making it a therapeutic target for diabetes, metabolic syndrome, autoimmune diseases, and cancer. Historically, drug discovery efforts focused on reversible full agonists of PPARγ for metabolic disorders; however, full receptor activation is associated with undesirable side effects. In the past decade, there has been a resurgence in research activity, primarily directed at strategies to partially activate or repress this target. In particular, many small covalent PPARγ ligands with various functionalities and therapeutic potential for several indications have been identified. Herein, we summarize the state of play in the PPARγ covalent modulator field. Critical chemical and structural biology related considerations relevant to covalent modulation of PPARγ are emphasized, with a focus on key insights that have enabled the first drug candidates to progress into the clinic.
More Related Videos
Related Concept Videos
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
GPCRs Regulate Adenylyl Cylase Activity
Ligand-Gated Ion Channel Receptor: Gating Mechanism
GPCR Desensitization
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...

