ArticlePharmaceutics2020
A Colon-Targeted Prodrug, 4-Phenylbutyric Acid-Glutamic Acid Conjugate, Ameliorates 2,4-Dinitrobenzenesulfonic Acid-Induced Colitis in Rats.
Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- ER Proteotoxic Stress Drives Mitochondrial Dysfunction in Heat-Stressed Intestinal Epithelial Cells.Cells · 2026Article
- Modifying microbially derived short chain fatty acids to promote health.The Journal of physiology · 2026Review
- 4-Phenylbutyric acid extends the gold time of uncontrolled hemorrhagic shock at high altitude by alleviating vital organ injury.Intensive care medicine experimental · 2025Article
- 4-Phenylbutyric Acid Reduces the Proliferation in Colon Cancer Cell Lines Through Modulating the Cell Cycle Regulatory Genes: An In Silico and In Vitro Approach.Cancer reports (Hoboken, N.J.) · 2025Article
- Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery.International journal of molecular sciences · 2025Review
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.Current pharmaceutical design · 2025Review
- The role and mechanism of β-catenin-mediated skeletal muscle satellite cells in osteoporotic fractures by Jian-Pi-Bu-Shen formula.Journal of molecular histology · 2024Article
- Modulation of Orosomucoid-like Protein 3 Activity in the Management of Inflammatory Bowel Disease.Journal of biotechnology and biomedicine · 2024Article
- 4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats.Croatian medical journal · 2023Article
- Advances in Oral Drug Delivery Systems: Challenges and Opportunities.Pharmaceutics · 2023Review
- Colon-Targeted Trans-Cinnamic Acid Ameliorates Rat Colitis by Activating GPR109A.Pharmaceutics · 2022Article
- Article
- The Role of 4-Phenylbutyric Acid in Gut Microbial Dysbiosis in a Mouse Model of Simulated Microgravity.Life (Basel, Switzerland) · 2022Article
- Article
- Novel drug delivery systems for inflammatory bowel disease.World journal of gastroenterology · 2022Review
- Dapsone Azo-Linked with Two Mesalazine Moieties Is a "Me-Better" Alternative to Sulfasalazine.Pharmaceutics · 2022Article
- Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases.Frontiers in molecular biosciences · 2022Review
- A Gut-Ex-Vivo System to Study Gut Inflammation Associated to Inflammatory Bowel Disease (IBD).Biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER-stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield 4-PBA-glutamic acid (PBA-GA) and 4-PBA-aspartic acid (PBA-AA) conjugates. The PBA derivatives were converted to 4-PBA in the cecal contents, and the conversion was greater with PBA-GA than that with PBA-AA. After oral administration of PBA-GA (oral PBA-GA), up to 2.7 mM PBA was detected in the cecum, whereas 4-PBA was not detected in the blood, indicating that PBA-GA predominantly targeted the large intestine. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon and substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was found to be as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably via the attenuation of ER stress in the inflamed colon.
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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.