{
  "id": 16149610,
  "title": "Small-molecule ACOD1 inhibition attenuates colitis and tumor growth through a shared myeloid mechanism, diverging from genetic deletion",
  "url": "https://urgent.news/2026/10/22/small-molecule-acod1-inhibition-attenuates-colitis-and-tumor-growth",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-22T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759827v1?rss=1"
  },
  "original_language": "en",
  "account": "Aconitate decarboxylase 1 (ACOD1) is an enzyme crucial for producing immunometabolite itaconate, which has been linked to anti-inflammatory actions in tissue damage. Research on ACOD1-deficient mice and itaconate supplementation in experiments has demonstrated its role as a brake on tissue inflammation. However, the small-molecule inhibitor ERG344, which suppresses itaconate synthesis, has shown surprising effects. In endotoxemic mice and inflamed colonic mucosa, ERG344 treatment, contrary to genetic-deletion studies, attenuated acute DSS colitis in an ACOD1-dependent manner. The inhibitor's action was associated with a reduced influx of immature monocytes early on and an accumulation of mature neutrophils. In syngeneic tumor models, ERG344 treatment prolonged survival and increased tumor-infiltrating lymphocytes and antigen-presenting dendritic cells. Through an extensive analysis of murine and human colitis scRNA-seq datasets, as well as a ten-model syngeneic tumor atlas, ACOD1 was found to mark interferon-stimulated immature monocytes and maturing neutrophils, and tracked independently of interferon and NF-{kappa}B signaling. It appears that ACOD1 acts through a common myeloid recruitment and maturation mechanism, suggesting that pharmacological ACOD1 inhibition could be a viable therapeutic strategy for both colitis and cancer.",
  "summary": "Aconitate decarboxylase 1 (ACOD1), the enzyme responsible for synthesis of the immunometabolite itaconate, is widely regarded as an anti-inflammatory brake on tissue damage based on Acod1-deficient mice and itaconate supplementation expermiments. ERG344, a small-molecule ACOD1 inhibitor, suppressed itaconate synthesis in endotoxemic mice and in inflamed colonic mucosa and, contrary to…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}