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Deconvolution01:20

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Deconvolution, also known as inverse filtering, is the process of extracting the impulse response from known input and output signals. This technique is vital in scenarios where the system's characteristics are unknown, and they must be inferred from the observable signals.
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Related Experiment Video

Updated: Feb 2, 2026

Laser Microdissection-Based Protocol for the LC-MS/MS Analysis of the Proteomic Profile of Neuromelanin Granules
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Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology.

Yu Ohki1, Hidetaka Sakurai2, Madoka Hoshino3

  • 1Rare Disease Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.

Cell Chemical Biology
|November 20, 2018
PubMed
Summary

Identifying the molecular targets of small molecules, or target deconvolution, is crucial for drug discovery. We developed perturbation-based proteomic correlation profiling (PPCP) to identify lanosterol synthase as a target of a TGF-β pathway inhibitor.

Keywords:
TGF-β pathway inhibitorcell line panelchemical proteomicsgene knockdownlanosterol synthasemass spectrometryperturbation-based proteomic correlation profilingphenotype-based drug discoveryradioactive compound binding assaytarget deconvolution

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Area of Science:

  • Proteomics
  • Chemical Biology
  • Drug Discovery

Background:

  • Target deconvolution is a significant challenge in phenotype-based drug discovery, hindering the identification of molecular targets for small molecules.
  • Understanding the precise molecular target is essential for optimizing drug efficacy and minimizing off-target effects.

Purpose of the Study:

  • To develop and validate a novel method for molecular target identification (target deconvolution).
  • To identify the molecular target of a transforming growth factor beta (TGF-β) pathway inhibitor.

Main Methods:

  • Developed perturbation-based proteomic correlation profiling (PPCP), a technique correlating protein quantity with compound binding activity under gene silencing.
  • Applied PPCP to cellular models to analyze proteomic changes in response to compound treatment and genetic perturbations.
  • Extended the PPCP approach to a panel of cell lines for broader applicability.

Main Results:

  • Successfully identified lanosterol synthase as the molecular target of a TGF-β pathway inhibitor using the PPCP method.
  • Demonstrated the utility of PPCP in accurately deconvoluting small molecule targets.
  • Validated the PPCP concept across a cell line panel, showcasing its versatility.

Conclusions:

  • Perturbation-based proteomic correlation profiling (PPCP) offers a powerful new strategy for molecular target deconvolution.
  • The identification of lanosterol synthase provides a specific target for TGF-β pathway modulation.
  • PPCP represents a valuable addition to the toolkit for advancing drug discovery and development.