Related Experiment Video

Updated: Jun 20, 2025

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
12:48

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation

Published on: August 21, 2017

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Carnosic Acid: A Novel Selective Inhibitor of ERAP1 by Direct Binding and Its Modulation of Antigen Processing and

Jiaqi Wu1, Zhao Li2, Xiaofan Liu1

  • 1School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.

Journal of Agricultural and Food Chemistry
|July 18, 2024
PubMed

Insights

A novel natural compound, carnosic acid, effectively inhibits ERAP1, a key target in autoimmune diseases like MHC-I-opathy. This discovery offers new therapeutic strategies for autoimmune conditions and cancer immunity.

Area of Science:

  • Biochemistry
  • Immunology
  • Pharmacology

Background:

  • Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a critical target for autoimmune diseases (MHC-I-opathy) and tumor immunity.
  • Developing effective ERAP1 inhibitors presents a significant challenge in therapeutic research.

Purpose of the Study:

  • To identify and characterize novel ERAP1 inhibitors from natural sources.
  • To investigate the binding mechanism and therapeutic potential of carnosic acid against ERAP1.

Main Methods:

  • High-throughput screening of food-derived natural products.
  • Biochemical assays to determine ERAP1 inhibitory activity and selectivity.
  • Molecular modeling to elucidate the binding mode of carnosic acid.
  • Cell-based assays using HLA-B27 models to validate therapeutic effects.

Main Results:

  • Carnosic acid, a food-derived compound, was identified as a potent and highly selective ERAP1 inhibitor.
  • Carnosic acid exhibits a unique binding mode within the ERAP1 active site's S1' pocket.
  • Inhibition of ERAP1 by carnosic acid reversed the ankylosing spondylitis (AS)-associated cellular phenotype in HLA-B27 models.

Conclusions:

  • Carnosic acid is a promising direct inhibitor of ERAP1 with therapeutic potential for MHC-I-opathy.
  • The distinct binding mechanism of carnosic acid provides insights for designing novel ERAP1 inhibitors.
  • This study highlights carnosic acid as a key therapeutic agent targeting ERAP1 in autoimmune diseases.
Keywords:
ERAP1ankylosing spondylitisantigen processing and presentationautoimmune diseasecarnosic acidselective inhibitortarget drug

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