ArticlePharmacological research2025
Pyrazolone-based ERO1 inhibitors in ERO1-driven triple-negative breast cancer and SEPN1-related myopathy: Structure-activity relationship and therapeutic potential.
Article in Pharmacological research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- ER proteostasis meets mitochondrial function: contact sites as hubs of communication and therapeutic targets.The FEBS journal · 2026Review
- Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline.Communications biology · 2026Article
- Selenoprotein N and SEPN1-Related Myopathies: Mechanisms, Models, and Therapeutic Perspectives.Biomolecules · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Endoplasmic reticulum oxidoreductin 1 alpha (ERO1A) is a disulfide oxidase that facilitates oxidative protein folding by reoxidizing protein disulfide isomerase (PDI), a process essential for maintaining endoplasmic reticulum (ER) homeostasis. Under ER stress, ERO1A expression is upregulated via the unfolded protein response (UPR), promoting cell survival. However, sustained ERO1A activity can impair proteostasis and contribute to disease. Notably, ERO1A is overexpressed in triple-negative breast cancer (TNBC), where it supports tumor growth and adaptation to hypoxia, and in SEPN1-related myopathy, a rare congenital muscle disorder linked to ER and oxidative stress. To investigate ERO1A as a therapeutic target, we conducted a structure-activity relationship (SAR) study of EN460-based pyrazolone inhibitors. Forty derivatives and three EN460 salts were synthesized to optimize potency and solubility. In vitro and cell-based assays revealed that effective inhibition required covalent binding to Cys397, interactions with Arg287 and Trp200, and distortion of the phenyl ring. While sulfonic acid substitution improved solubility, it abolished activity by disrupting key interactions. The most potent compound, I29, featuring a mono ortho-fluorine substitution, demonstrated improved inhibitory activity (IC₅₀ = 2.6 µM) and efficacy in preclinical models of TNBC and SEPN1-related myopathy. These findings highlight ERO1A's pathological role in cancer and congenital muscle disease and support its inhibition as a promising therapeutic strategy for conditions characterized by chronic ER and oxidative stress.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.