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Related Concept Videos

Drug Discovery: Overview01:26

Drug Discovery: Overview

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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...
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The development of flow cytometry techniques began in 1934 with initial attempts by Andrew Moldavan, a bacteriologist who counted the cells in a flowing capillary system. Moldavan pumped cells through a capillary tube focused under a microscope for visualization. The invention of photometry allowed the measurement of differentially-stained cells, and Louis Kamentsky developed the first multiparameter flow cytometer in 1965 to identify and count the cancer cells in cervical tissue specimens.
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Renal Drug Excretion: Effect of Urine pH, Flow Rate, and Drug pKa01:22

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The pH of urine, the drug's pKa, and the urine flow rate are vital parameters for drug reabsorption and excretion. Urinary pH varies between 4.6 and 8.0 and is influenced by diet, drug intake, and the patient's pathophysiology. It affects a drug's ionization state and reabsorption. For instance, carbohydrate-rich food produces alkaline urine promoting drug excretion, while proteins and certain medications like ascorbic acid lead to acidic urine enhancing reabsorption.
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Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

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Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
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Background and Environment Affect Phenotype02:27

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Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
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Gene Flow02:39

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Gene flow is the transfer of genes among populations, resulting from either the dispersal of gametes or from the migration of individuals.
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Automation of the Micronucleus Assay Using Imaging Flow Cytometry and Artificial Intelligence
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A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery.

John Joslin1, James Gilligan1, Paul Anderson1

  • 11 Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.

SLAS Discovery : Advancing Life Sciences R & D
|May 31, 2018
PubMed
Summary
This summary is machine-generated.

Automated flow cytometry enables high-throughput phenotypic drug discovery by processing complex assays. This robust platform accelerates the identification of drug candidates for various diseases, advancing them into clinical development.

Keywords:
drug discoveryhigh-throughput flow cytometryhigh-throughput screeningphenotypic screening

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Area of Science:

  • Drug discovery and development
  • Biotechnology
  • Pharmacology

Background:

  • High-throughput screening (HTS) aims to automate compound library screening for drug optimization.
  • Phenotypic screening is valuable for drug identification without target knowledge, using disease-relevant assays.
  • Current complex assays are limited by slow, low-throughput methods despite automation and imaging advancements.

Purpose of the Study:

  • To develop an automated workflow for processing complex phenotypic assays using flow cytometry.
  • To enhance the throughput and robustness of phenotypic drug discovery.
  • To showcase diverse applications of automated flow cytometry in drug discovery programs.

Main Methods:

  • Development of a dedicated automated workflow for complex phenotypic assays.
  • Implementation of flow cytometry for high-throughput sample processing.
  • Validation of the system's performance over five years across multiple drug discovery programs.

Main Results:

  • Achieved a throughput of 50,000 wells per day.
  • Established a fully automated platform for robust phenotypic drug discovery.
  • Successfully utilized the system in various disease areas, advancing molecules to preclinical and clinical stages.

Conclusions:

  • Automated flow cytometry significantly enhances the efficiency and scope of phenotypic drug discovery.
  • The developed platform enables rapid identification and advancement of drug candidates.
  • This technology supports diverse drug discovery approaches across multiple therapeutic areas.