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Triazole-based STING inhibitors.

Anju Singh1, Leonard Barasa1, Leo DeOrsey1

  • 1Program in Chemical Biology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

Bioorganic & Medicinal Chemistry
|November 16, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed ASF24, a novel triazole-based compound that potently inhibits the STING signaling pathway. This discovery offers a promising new therapeutic strategy for inflammatory diseases linked to STING activation.

Keywords:
Covalent inhibitorInflammationNitrofuranSTINGTriazole

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Area of Science:

  • Immunology
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Aberrant activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is implicated in autoimmune and autoinflammatory diseases like ALS, SLE, AGS, and SAVI.
  • Development of STING inhibitors is a key therapeutic strategy for these conditions.

Purpose of the Study:

  • To design and develop novel STING inhibitors based on a triazole scaffold.
  • To identify potent and selective inhibitors for targeting STING-mediated inflammatory diseases.

Main Methods:

  • Synthesis and chemical characterization of a series of triazole-based analogues.
  • In vitro evaluation of STING signaling inhibition potency (IC50 determination).
  • Assessment of in vivo efficacy and selectivity of lead compounds.

Main Results:

  • Identification of ASF24, a novel triazole-based compound with potent STING signaling inhibition (IC50 = 0.49 μM).
  • The nitrofuran warhead in previous inhibitors like LB244 demonstrated superior potency and proteome-wide selectivity.
  • ASF24 represents a promising scaffold for further therapeutic development.

Conclusions:

  • ASF24 is a highly potent inhibitor of STING signaling.
  • The developed triazole-based scaffold holds promise for developing new therapeutics targeting STING-mediated inflammatory diseases.