Related Experiment Video
Updated: Feb 20, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Structure-Activity Relationship Studies toward the Optimization of First-In-Class Selective Small Molecule Agonists
Kenneth J Wilson1, Maria Esteban-Lopez2, Courtney Myhr2
1National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Abstract:
A dose-response quantitative high-throughput screening of 147,334 small molecule compounds using a human Relaxin/Insulin-like Family Peptide Receptor 2 (RXFP2)-transfected HEK293T-RXFP2 cell line identified compound 5 with modest Insulin-Like3 (INSL3) agonist activity. An extensive structure-activity relationship (SAR) study was undertaken to improve potency, efficacy, and physical/metabolic properties of the series, resulting in the discovery of compound 68. This compound represents the first-in-class small molecule full agonist of RXFP2 that exhibits nanomolar potency and favorable pharmacokinetic characteristics, including high systemic exposure in vivo. Based on these findings, compound 68 was selected as the lead preclinical candidate for investigating the role of RXFP2 activation in bone remodeling and other physiological systems in vitro and in vivo.
More Related Videos
08:21Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
Published on: June 28, 2019
09:39Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Related Concept Videos
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
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...
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with...
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
GPCRs Regulate Adenylyl Cylase Activity