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Updated: Jul 2, 2026
07:10
In vivo Imaging Method to Distinguish Acute and Chronic Inflammation
Published on: August 16, 2013
A druggable redox switch on SHP1 controls macrophage inflammation
Mei Ying Ng1,2, Meredith N Nix3,4, Guangyan Du3
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Biorxiv : the Preprint Server for Biology
|February 27, 2026
Summary
Researchers identified druggable cysteine sites on immune proteins, discovering a new way to control macrophage cytokine responses. This work opens avenues for developing novel therapeutics targeting immune cell regulation.
Area of Science:
- Immunology
- Biochemistry
- Pharmacology
Background:
- Immunological proteins are key disease targets, but many are undrugged.
- Redox modification of cysteine residues regulates immune cell function, especially macrophage cytokine responses.
Purpose of the Study:
- To develop a strategy for discovering and functionalizing redox-regulated cysteines on immunological proteins.
- To identify novel cysteine sites for targeted small-molecule drug development.
Main Methods:
- Deep redox proteomics was used to identify in vivo redox-regulated cysteines.
- A novel cysteine activation site on SHP1 was discovered and targeted.
- A selective covalent agonist (SCA) was developed to target Cys102 on SHP1.
Main Results:
- 788 in vivo redox-regulated cysteines were annotated across immune-relevant protein domains.
- A novel cysteine activation site on SHP1 (Cys102) was identified.
- SCA selectively activated SHP1, antagonizing IRAK signaling and reducing pro-inflammatory cytokine production in macrophages.
Conclusions:
- A druggable cysteine redox switch controlling macrophage cytokine responses was identified.
- A compendium of redox-regulated sites was generated for therapeutic development.
- This approach enables cysteine-directed pharmacology for immunological targets.
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