Related Experiment Video

Updated: Feb 5, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

1.3K

Discovery of Potent Disheveled/Dvl Inhibitors Using Virtual Screening Optimized With NMR-Based Docking Performance

Kiminori Hori1, Kasumi Ajioka2, Natsuko Goda1

  • 1Laboratory of Structural Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.

Frontiers in Pharmacology
|September 21, 2018
PubMed

Insights

Researchers identified novel Wnt pathway inhibitors targeting Disheveled (Dvl) to combat chemo-resistant cancer stem cells (CSCs). These compounds show promise for treating triple-negative breast cancer (TNBC).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Cancer stem cells (CSCs) drive tumor growth and chemoresistance in solid tumors.
  • The Wnt/β-catenin pathway is crucial for CSC self-renewal and tumorigenesis.
  • Mammalian Disheveled (Dvl) is a key regulator in the Wnt pathway and a potential drug target.

Purpose of the Study:

  • To identify novel inhibitors of the Dvl PDZ domain.
  • To evaluate the potential of these inhibitors for anti-cancer therapy, particularly for triple-negative breast cancer (TNBC).

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy to analyze Dvl1-PDZ interactions.
  • Virtual screening (VS) using GOLD software to identify potential drug candidates.
  • NMR titration experiments to validate binding of new compounds.
  • Cell proliferation assays using BT-20 TNBC cells.

Main Results:

  • Identified over 1,700 compounds with higher binding scores than a known inhibitor.
  • Five novel compounds (NPL-4001, 4004, 4011, 4012, 4013) showed significant interaction with Dvl1-PDZ via NMR.
  • These compounds demonstrated partial inhibition of BT-20 cell proliferation.

Conclusions:

  • The identified compounds are potent Wnt pathway inhibitors targeting Dvl.
  • These novel inhibitors hold potential for developing new anti-TNBC therapies.
Keywords:
NMR-derived docking performance indexWnt signalingprotein–protein interaction inhibitortriple negative breast cancervirtual screening

More Related Videos

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

5.5K
NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode09:19

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

3.8K

Related Concept Videos

Virtual Work01:20

Virtual Work

The principle of virtual work states that if a body is in static and dynamic equilibrium, then the sum of all the virtual work done by all external forces and couple moments for any given virtual displacement must be zero.
In static equilibrium, a body can experience an imaginary or virtual movement, such as displacement or rotation. The virtual work done by a force is equal to the dot product of force and virtual displacement in the direction of the force. When it comes to virtually rotating a...
1.4K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Drug Discovery: Overview01:26

Drug Discovery: Overview

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...
11.6K
¹³C NMR: ¹H–¹³C Decoupling01:04

¹³C NMR: ¹H–¹³C Decoupling

The probability of having two carbon-13 atoms next to each other is negligible because of the low natural abundance of carbon-13. Consequently, peak splitting due to carbon-carbon spin-spin coupling is not observed in spectra. However, protons up to three sigma bonds away split the carbon signal according to the n+1 rule, resulting in complicated spectra.
A broadband decoupling technique is used to simplify these complex, sometimes overlapping, signals. Broadband decoupling relies on a...
1.8K
Principle of Virtual Work: Problem Solving01:13

Principle of Virtual Work: Problem Solving

The principle of virtual work is an essential concept in the field of mechanics and engineering. This is used to solve problems related to the equilibrium of a structure or system. It is based on the assumption that if a system is in equilibrium, the work done by all the forces during a virtual displacement is zero. This principle is applied by considering virtual displacements of the system and the corresponding work done by internal and external forces.
To apply the principle of virtual work,...
1.7K
Optimal Foraging00:48

Optimal Foraging

How animals obtain and eat their food is called foraging behavior. Foraging can include searching for plants and hunting for prey and depends on the species and environment.
13.8K