New drugs to calm inflammation by targeting a switch on the SHP-1 protein

Targeting SHP-1 through a newfound metabolite-regulated cysteine activation site

NIH-funded research Dana-Farber Cancer Inst · NIH-11144388

Researchers are developing small molecules that modify a specific spot on a protein in immune cells to reduce harmful inflammation.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionDana-Farber Cancer Inst NIH-funded
Lab location1 site (Boston, United States)
Project IDNIH-11144388 on NIH RePORTER

What this research studies

Researchers discovered that a natural metabolite called itaconate attaches to a particular cysteine on the SHP-1 protein in macrophages, which helps control inflammatory signals. They use advanced mass spectrometry, protein structure studies, and cell-based assays in mouse and human macrophages to understand how that site works. The team is designing and testing drug-like itaconate-mimetic compounds to selectively modify that cysteine and lower cytokine production. Work combines chemistry, structural biology, and functional immune tests to find compounds with the best potency and specificity.

Who could benefit from this research

Good fit: People with conditions driven by macrophage-mediated inflammation, such as certain autoimmune or inflammatory diseases, would be the most likely future candidates for therapies developed from this work.

Not a fit: Patients whose illnesses are not driven by macrophage cytokines or who need immediate standard treatments are unlikely to benefit from these early-stage efforts.

Why it matters

Potential benefit: If successful, this work could lead to new anti-inflammatory drugs that reduce damaging cytokine release in diseases driven by overactive macrophages.

How similar studies have performed: Prior studies have shown that itaconate can reduce macrophage-driven inflammation, but creating selective drug-like mimics that target this specific SHP-1 cysteine is a novel and unproven approach.

Where this research is happening

Boston, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.