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Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...

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Related Experiment Video

Updated: Jun 16, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
10:05

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Single cell network profiling (SCNP): mapping drug and target interactions.

Todd M Covey1, Santosh Putta, Alessandra Cesano

  • 1Nodality Inc., South San Francisco, California, USA.

Assay and Drug Development Technologies
|February 18, 2010
PubMed
Summary
This summary is machine-generated.

Single cell network profiling (SCNP) measures drug effects on cell signaling in whole blood. This method aids in selecting drug candidates and designing clinical trials for better target coverage.

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Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation
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Last Updated: Jun 16, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
10:05

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation
07:57

Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation

Published on: August 21, 2019

Area of Science:

  • Pharmacology
  • Immunology
  • Biotechnology

Background:

  • Assessing small molecule inhibitor efficacy is crucial for drug development and clinical dosing.
  • Single cell network profiling (SCNP) offers a method to analyze compound effects on cellular signaling pathways.
  • Current methods often use fractionated cells, potentially altering drug response measurements.

Purpose of the Study:

  • To apply SCNP in whole blood to measure the potency and selectivity of Janus kinase (Jak) inhibitors.
  • To compare SCNP results in whole blood versus peripheral blood mononuclear cells (PBMC).
  • To evaluate SCNP's utility for preclinical drug selection and clinical trial design.

Main Methods:

  • Utilized multiparameter flow cytometry for SCNP analysis.
  • Applied SCNP to a panel of Jak/Stat signaling inhibitors in whole human blood.
  • Used a combination of cytokines (GM-CSF, IL-2, CD40L) to stimulate distinct immune cell subsets.
  • Measured compound potency and selectivity across different cell types and signaling pathways.

Main Results:

  • SCNP successfully measured compound effects on multiple signaling cascades in specific cell subsets within whole blood.
  • Jak/Stat inhibitors showed varying potency and selectivity profiles against Jak2, Jak3, and off-target pathways.
  • A general loss of compound potency was observed when SCNP was performed in whole blood compared to fractionated PBMC.
  • Robust IC50 values were obtained even from rare cell subpopulations.

Conclusions:

  • SCNP in whole blood provides a physiologically relevant environment for assessing drug candidate potency and selectivity.
  • This approach facilitates the preclinical selection of lead molecules.
  • In vitro IC50 measurements in whole blood can inform target plasma concentrations for clinical studies and guide dose selection in early phase trials.
  • SCNP enables a shift towards biologically active dose-based clinical trial design.