Related Experiment Video

Updated: Sep 8, 2025

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
08:35

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

5.8K

Structure-Based Discovery of a Series of NSD2-PWWP1 Inhibitors

Na Li1,2, Hong Yang3, Ke Liu4

  • 1Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P. R. China.

Journal of Medicinal Chemistry
|June 15, 2022
PubMed

Insights

Researchers developed a potent and selective inhibitor (compound 38) targeting the NSD2-PWWP1 domain, an oncoprotein implicated in various cancers. This discovery offers a chemical probe for studying NSD2 regulation and developing new anticancer drugs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • The protein lysine methyltransferase NSD2 is an oncoprotein overexpressed or mutated in numerous cancers.
  • NSD2's domains, including the SET catalytic domain and PWWP domains, are crucial for its function in regulating gene expression.
  • Targeting NSD2 presents a promising strategy for anticancer drug development.

Purpose of the Study:

  • To develop novel inhibitors targeting the NSD2-PWWP1 domain.
  • To identify a potent and selective chemical probe for investigating NSD2 function.
  • To lay the groundwork for future NSD2-targeted therapeutic strategies.

Main Methods:

  • Structure-based drug design and optimization were employed to develop NSD2-PWWP1 inhibitors.
  • A series of inhibitors were synthesized and evaluated.
  • Compound 38 was identified as a potent and selective inhibitor through biological evaluation.

Main Results:

  • A potent inhibitor, compound 38, was developed with high selectivity for the NSD2-PWWP1 domain.
  • Compound 38 demonstrated the ability to bind to NSD2-PWWP1.
  • The inhibitor was shown to modulate the expression of NSD2-regulated genes.

Conclusions:

  • Compound 38 serves as a valuable chemical probe for understanding NSD2 regulation via PWWP1 interaction.
  • This research provides a foundation for developing novel anticancer therapeutics targeting NSD2.

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

5.0K
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

3.4K

Related Concept Videos

Protein-protein Interfaces02:04

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
13.2K
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...
8.7K