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Related Concept Videos

Dose Response Curve: Conventional Versus Nonmonotonic01:21

Dose Response Curve: Conventional Versus Nonmonotonic

The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...
Dose-Response Relationship: Overview01:03

Dose-Response Relationship: Overview

Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
Pharmacodynamic Models: Direct Effect Model and Indirect Response Model01:29

Pharmacodynamic Models: Direct Effect Model and Indirect Response Model

Pharmacodynamic models are essential tools in understanding the relationship between drug concentrations and their effects on biological systems. By characterizing the dynamics of drug action, these models guide dose selection, optimize therapeutic efficacy, and inform the development of new drugs. Two major classes of pharmacodynamic models include direct effect and indirect response models.Direct Effect ModelsDirect effect models describe the immediate relationship between drug concentration...
Pharmacodynamic Models: Additive and Proportional Drug Effect Model01:09

Pharmacodynamic Models: Additive and Proportional Drug Effect Model

Drug response models describe how pharmacological agents interact with biological systems to produce measurable effects. Baseline responses are inherent physiological activities without a drug significantly influencing the observed pharmacological outcomes. Depending on the drug response model employed, these baseline responses may combine with the drug's effect in either an additive or proportional manner.Additive Drug Response ModelIn the additive model, the drug effect is independent of the...
Dose-Response Relationship: Potency and Efficacy01:22

Dose-Response Relationship: Potency and Efficacy

The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it produces...
Dose-Response Relationship: Selectivity and Specificity01:25

Dose-Response Relationship: Selectivity and Specificity

Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...

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Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays
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Dose-response modeling of high-throughput screening data.

Fred Parham1, Chris Austin, Noel Southall

  • 1National Institutes of Health (NIH)/National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA. parham@niehs.nih.gov

Journal of Biomolecular Screening
|October 16, 2009
PubMed
Summary
This summary is machine-generated.

The National Toxicology Program developed a statistical method to identify toxic compounds using high-throughput screening (HTS) assays. This approach analyzes concentration-response data to accurately classify chemical effects on cells.

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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
11:38

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

Published on: May 10, 2016

Area of Science:

  • Toxicology
  • Computational Biology
  • Biostatistics

Background:

  • The National Toxicology Program (NTP) is establishing a high-throughput screening (HTS) program.
  • HTS aims to prioritize chemical testing, elucidate mechanisms of action, and predict human toxicity.
  • Distinguishing positive from negative compound results in HTS assays is crucial for relating findings to in vivo toxicity.

Purpose of the Study:

  • To develop and present a statistical approach for identifying positive and negative compounds in HTS cytotoxicity assays.
  • To normalize HTS data, accounting for positional bias on assay plates.
  • To analyze concentration-response relationships and assess reproducibility.

Main Methods:

  • Screening of 1353 compounds for concentration-response effects across 9 human and 4 rodent cell types.
  • Development of data normalization methods to correct for well-plate location bias.
  • Application of statistical tests to identify significant concentration-response relationships and evaluate reproducibility.

Main Results:

  • A robust statistical methodology was established for analyzing HTS cytotoxicity data.
  • The approach effectively normalizes data and identifies concentration-dependent effects.
  • Methods for assessing the reproducibility of HTS assay results were presented.

Conclusions:

  • The developed statistical approach provides a reliable method for classifying compounds in HTS cytotoxicity assays.
  • Accurate identification of compound activity is essential for the NTP's HTS program goals.
  • This work contributes to the advancement of predictive toxicology models.