Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

595
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
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...
595
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

5.0K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
5.0K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
1.9K
Drug Discovery: Overview01:26

Drug Discovery: Overview

7.5K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.5K
Quantitative Aspects of Drug-Receptor Interaction01:30

Quantitative Aspects of Drug-Receptor Interaction

934
The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower...
934
Spare Receptors01:30

Spare Receptors

3.5K
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
3.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Complex Distribution Phenomena and Plastic Binding of Test Chemicals in Cell Culture Experiments: Exemplification by Tebufenpyrad.

International journal of molecular sciences·2026
Same author

New approach methodologies as first tier in an integrated approach to testing and assessment for non-genotoxic carcinogens.

ALTEX·2026
Same author

Discovery and Optimization of Potent and Subtype-Selective Urea-Derived Na<sub>V</sub>1.8 Inhibitors.

ACS medicinal chemistry letters·2026
Same author

Stakeholder input towards further refinement and consolidation of the alternative safety profiling algorithm (ASPA) for next generation risk assessment (NGRA).

ALTEX·2026
Same author

T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.

Circulation research·2026
Same author

Quantitative systems toxicology approach that integrates PBPK and core hepatic metabolism: a case study with valproic acid.

Frontiers in pharmacology·2026
Same journal

Analytical performance of poly(L-cysteine) modified pencil graphite electrode for dapsone detection.

Journal of pharmacological and toxicological methods·2026
Same journal

Corrigendum to "Nonclinical cardiovascular safety assessment of thioridazine: Impact of heart rate, body temperature, and choice of species" [Journal of Pharmacological and Toxicological Methods, Volume 115 (2022), 107167].

Journal of pharmacological and toxicological methods·2026
Same journal

Rapid and sensitive quantification of pemetrexed in human plasma by LC-MS/MS using a stable isotope-Labeled internal standard for therapeutic drug monitoring.

Journal of pharmacological and toxicological methods·2026
Same journal

The INSPIRE doctoral network in safety pharmacology - Looking back and ahead.

Journal of pharmacological and toxicological methods·2026
Same journal

NADES-assisted sustainable extraction of total protein content from Achyranthes bidentata seeds and their biochemical characterization.

Journal of pharmacological and toxicological methods·2026
Same journal

Non-invasive, home cage digital monitoring for improved safety pharmacology assessments in drug development: ICH S7A update considerations.

Journal of pharmacological and toxicological methods·2026
See all related articles

Related Experiment Video

Updated: Jun 6, 2025

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

2.4K

Predicting clinical outcomes from off-target receptor interactions using Secondary Intelligence™.

Will S Redfern1, Chris E Pollard1, Mark Holbrook1

  • 1Certara Predictive Technologies, Certara UK Limited, Level 2-Acero, 1 Concourse Way, Sheffield S1 2BJ, United Kingdom.

Journal of Pharmacological and Toxicological Methods
|November 22, 2024
PubMed
Summary
This summary is machine-generated.

Predicting adverse drug effects from off-target activity is now possible. A new quantitative framework compares drug concentration to receptor binding, moving from opinion to evidence-based risk assessment for safer drug development.

Keywords:
In silicoNAMsSafety pharmacologySecondary pharmacology

More Related Videos

Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

18.4K
Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions
06:01

Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions

Published on: January 7, 2019

7.2K

Related Experiment Videos

Last Updated: Jun 6, 2025

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

2.4K
Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

18.4K
Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions
06:01

Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions

Published on: January 7, 2019

7.2K

Area of Science:

  • Pharmacology and Drug Discovery
  • Toxicology and Risk Assessment
  • Computational Chemistry

Background:

  • Adverse effects from unintended drug interactions (off-target activity) pose a significant challenge in drug development.
  • Current risk assessment for off-target effects is often subjective and lacks a standardized quantitative approach.
  • Understanding the relationship between drug concentration and receptor occupancy is crucial for predicting therapeutic efficacy and adverse events.

Purpose of the Study:

  • To develop a quantitative framework for predicting adverse effects arising from drug off-target activity.
  • To establish a consistent, evidence-based approach for assessing the risks associated with secondary pharmacology.
  • To enable reliable risk assessment across different receptors, compounds, and evaluators.

Main Methods:

  • A quantitative method was developed comparing expected plasma concentration of test compounds to their off-target activity.
  • This comparison was benchmarked against reference drugs targeting specific receptors for therapeutic efficacy.
  • Data for over 30 drugs at 100 receptors (172 modulations) were curated and evaluated using the unbound plasma concentration to Ki ratio as a surrogate for receptor occupancy.

Main Results:

  • A quantitative framework was established for consistent risk assessment of off-target interactions.
  • The approach shifts secondary pharmacology assessment from an opinion-based to an evidence-based methodology.
  • Proof-of-principle was demonstrated for α1A-adrenoceptor antagonism, linking it to postural hypotension.

Conclusions:

  • The developed quantitative framework provides a robust method for predicting adverse effects from off-target drug activity.
  • This evidence-based approach enhances the consistency and reliability of drug safety assessments.
  • The methodology represents a significant advancement in the field of secondary pharmacology.