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ibuprofen + arginine (Spedifen / Zafen / Espedifen)

✓ Approved

Zambon · PTGS1 · Small Molecule

What is ibuprofen + arginine?

ibuprofen + arginine is a small molecule developed by Zambon. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesSpedifen, Zafen, Espedifen
CompanyZambon
Drug ClassSmall Molecule
Molecular TargetPTGS1, PTGS2
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Zambon

Mechanism of Action

Molecular Targets

ibuprofen + arginine acts on 2 molecular targets:

PTGS1prostaglandin-endoperoxide synthase 1 (COX3, PCOX1)
PTGS2prostaglandin-endoperoxide synthase 2 (GRIPGHS, hCox-2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

ibuprofen + arginine is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Gastrointestinal disordersAbdominal pain✓ Approved
Hepatobiliary disordersHepatitis✓ Approved

Related Research Articles

PubMedBioresource technology2026-07-25

Metabolic flux reprogramming and protein engineering drive efficient l-arginine biosynthesis.

He Shengyang S, Sheng Qi Q, Men Gang G, Zhao Chunguang C et al.

l-arginine is widely used in food, feed, pharmaceutical, and cosmetic industries. However, its industrial-scale biosynthesis is limited by insufficient coordination between metabolic regulation, pathway engineering, and fermentation optimization. In this study, an enzyme-constrained model (ec_iML1515) was used to identify 11 gene targets affecting l-arginine production. Based on these targets, metabolic reprogramming was performed in strain Arg4 to rebalance precursor pools (oxaloacetate, aspartate, and citrulline), generating strain Arg10 with an l-arginine titer of 87.24 g/L. Subsequently, the rate-limiting enzyme argininosuccinate synthetase (ArgG) was engineered to the optimal mutant ArgGY131F/K132R and genomically integrated to construct the strain Arg11, increasing the l-arginine titer to 94.80 g/L while reducing aspartate accumulation 7.6-fold to 1.1 g/L. Finally, after the optimization of fermentation temperature and pH, the l-arginine titer, yield, and productivity of strain Arg11 were 114.18 g/L, 0.57 g/g, and 2.27 g/L/h, respectively, in a 3-m3 fermenter, achieving the best performance reported to date.

PMID 42498017
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PubMedJournal of clinical lipidology2026-07-25

A novel VPS4A variant drives lipotoxicity underlying CIMDAG syndrome.

Gupta Apurva A, Mathuria Yogendra Pratap YP, Jain Buddhi Prakash BP, Gupta Shailesh Kumar SK et al.

Cerebellar hypoplasia, impaired intellectual development, congenital microcephaly, dystonia, anemia, and growth retardation (CIMDAG) syndrome is caused by variants in VPS4A. We report a 5-year-old Nepalese boy with classical CIMDAG features, including developmental delay, microcephaly, dystonia, cataracts, dyserythropoietic anemia, and growth retardation. Magnetic resonance imaging showed mild cerebellar atrophy. Trio exome sequencing identified a homozygous VPS4A variant (c.863G>A; p.Arg288Gln), predicted to be deleterious. Structural analyses revealed disruption of a conserved Arginine-288 residue within the ATPases associated with diverse cellular activities domain, leading to loss of stability and increased disorder. The VPS4A-p.Arg288Gln variant showed enhanced aggregation and reduced interaction with LC3B (microtubule-associated protein 1 light chain 3 beta), impairing its localization to lipid droplets. Proband fibroblasts exhibited increased lipid accumulation, elevated free fatty acids, and higher reactive oxygen species levels, indicative of lipotoxic stress. Together, these findings demonstrate that a novel pathogenic VPS4A variant drives structural destabilization and lipotoxicity, providing mechanistic insight into lipid homeostasis perturbations in CIMDAG syndrome.

PMID 42498620
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PubMedOncology research2026-07-25

Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.

Wan Zixin Z, Quan Jingdan J, Qiu Yue Y, Zhang Zhiwei Z

Gastric cancer (GC) is one of the malignant tumors with high incidence and mortality worldwide. It has concealed early symptoms, poor prognosis for advanced patients, and limited efficacy of conventional treatments. Metabolic reprogramming is a core hallmark of cancer, among which amino acid metabolic reprogramming plays a critical regulatory role in the initiation and progression of GC. By linking intracellular energy supply, biosynthetic demands, and tumor microenvironment remodeling, it participates in immune escape, redox homeostasis maintenance, and therapeutic resistance. Dysregulation of key amino acids, including arginine, tryptophan, glutamine, branched-chain amino acids, serine/glycine, and aspartic acid, as well as altered expression and activity of rate-limiting enzymes and key catalytic enzymes, collectively drive the proliferation, invasion, metastasis, and stemness maintenance of GC cells. These metabolic enzymes can serve as potential biomarkers for the diagnosis and prognosis of GC, and are also important targets for precision therapy. At present, progress has been made in the development of inhibitors targeting key enzymes in amino acid metabolism. Single-target therapy or its combination with chemotherapy and immunotherapy has shown promising application prospects, but challenges such as clinical translation bottlenecks and unclear drug resistance mechanisms still exist. This review systematically summarizes the roles and molecular mechanisms of key amino acid metabolic enzymes in the occurrence and development of GC, and sorts out the research status of related targeted therapies, so as to provide references for basic research and clinical translation of metabolic precision therapy for GC.

PMID 42500565
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PubMedPsychoneuroendocrinology2026-07-25

Innate anxiety in rats determines vulnerability to social fear conditioning and social fear memory.

Masís-Calvo Marianella M, Rappeneau Virginie V, Neumann Inga D ID

Social anxiety disorder (SAD) involves excessive fear of social situations and can be induced by social trauma. However, the underlying mechanisms of individual differences in the formation of social fear memory remain unclear. To address this gap, we adapted our mouse social fear conditioning paradigm for rats (rSFC) and compared adult male rats selectively bred for high (HAB) or low (LAB) anxiety-related behaviour and non-selected controls (NAB). HAB and LAB rats are established as a model displaying genetically determined extremes in socio-emotional behaviours. Conditioned HAB, LAB, and NAB rats all developed social fear, but with line-specific persistence. During a social fear discrimination test, HAB and LAB rats expressed social fear 24 h after acquisition, while NAB rats only showed transient social fear (up to 6 h), indicating reduced susceptibility to social trauma. Importantly, only HAB rats showed individual social fear memory, with reduced social investigation of the familiar rat encountered during social fear acquisition ("known") versus a novel ("unknown") rat. Blockade of brain V1a receptors after social fear acquisition slightly reduced generalised social fear in HAB rats and abolished their individual social fear memory, whereas central infusion of arginine vasopressin (AVP) modestly reduced generalised social fear in LAB rats. Additionally, rSFC induced a rapid corticosterone response, which was more pronounced in NAB than HAB rats. Blocking glucocorticoid synthesis before social fear acquisition slightly reduced generalised social fear in HAB rats. These findings demonstrate that innate anxiety determines the long-term formation of individual social fear memory, as assessed after a 24-h retention interval, in adult male rats and support rSFC as a useful experimental model to investigate selected neurobiological mechanisms relevant to SAD.

PMID 42497747
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PubMedOncology research2026-07-25

miR-320d Is Associated with Reduced Nasopharyngeal Carcinoma Progression, Potentially through the NF-κB/IL-8 Axis-Mediated Inhibition of Neutrophil Extracellular Trap Formation.

Liu Liu L, Liu Jie J, Ning Shuangchen S, Wang Jin J et al.

Objectives: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck malignancy in which post-treatment recurrence and distant metastasis remain major contributors to poor clinical outcomes. Although microRNAs are important post-transcriptional regulators of tumor progression, the role of miR-320d in NPC remains incompletely understood. This study evaluated the biological role of miR-320d and explored whether it is involved in regulating neutrophil extracellular trap (NET) formation through the nuclear factor kappa-B (NF-κB)/interleukin-8 (IL-8) signaling axis. Methods: miR-320d was overexpressed in NPC cell lines S18 and 5-8F, and cell viability, migration, and invasion were evaluated. Integrated transcriptomic and proteomic analyses were performed to identify miR-320d-regulated genes, proteins, and pathways. Western blotting, immunohistochemistry, and immunofluorescence analyses were used to validate NET-associated proteins, including glycoprotein Ib platelet subunit alpha (GP1BA), histone deacetylase 10 (HDAC10), and fibrinogen gamma chain (FGG), as well as the expression of NET formation markers, including peptidyl arginine deiminase 4 (PADI4), myeloperoxidase (MPO), and neutrophil elastase (NE); and key components of the NF-κB/IL-8 axis. Results: miR-320d overexpression significantly inhibited the viability, migration, and invasion of both S18 and 5-8F cells. Multi-omics analyses indicated that miR-320d-regulated molecules were mainly enriched in NET-related pathways. Consistently, miR-320d reduced the expression of GP1BA, HDAC10, FGG, PADI4, MPO, and NE. Mechanistically, miR-320d suppressed NF-κB signaling, as shown by decreased phosphorylated NF-κB (p-NF-κB) and total NF-κB levels, and reduced IL-8 secretion in NPC cells. Conclusion: miR-320d may suppress NPC progression, at least in part, by attenuating NF-κB/IL-8-associated NET formation. These findings suggest that the miR-320d/NF-κB/IL-8/NET regulatory axis may participate in NPC progression and may warrant further translational investigation.

PMID 42500573
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PubMedKidney international2026-07-25

IL-33 as a component of neutrophil extracellular traps mediates contrast-induced acute kidney injury by promoting ferroptosis in tubular epithelial cells.

Ma Mengqing M, Zhang Hao H, Deng Weijuan W, Du Xia X et al.

Contrast-induced acute kidney injury (CIAKI) is a leading cause of hospital-acquired kidney dysfunction, yet its immune-mediated pathogenic mechanisms remain poorly defined. Neutrophil extracellular traps (NETs) have been implicated in acute kidney injury. However, whether contrast agents directly induce NETs formation and whether NETs drive tubular ferroptosis through IL-33 has not been investigated. A prospective cohort of 330 patients undergoing coronary angiography was enrolled, with serial measurement of circulating NETs markers (myeloperoxidase, neutrophil elastase) and IL-33 at pre-contrast, two- and 12-hour time points. A murine CIAKI model was established in wild-type, peptidyl arginine deaminase 4 (PAD4) -knockout, and IL-33-knockout mice, and single-cell transcriptomic profiling of CIAKI kidneys was performed. In vitro, the serine/threonine kinase IKKα- and β-catenin-overexpressing and knockdown HK-2 cells were stimulated with iodixanol-induced NETs to evaluate how NETs regulate ferroptosis through IL-33-mediated modulation of IKKα and β-catenin. CIAKI occurred in 12.1% (40/330) of patients. Circulating NETs markers and IL-33 were significantly elevated at two and 12 hours post-contrast in CIAKI compared with non-CIAKI patients. Single-cell transcriptomics identified neutrophils as the predominant source of IL-33 in CIAKI kidneys and revealed enrichment of NET formation and ferroptosis pathways. In vivo, PAD4 and IL-33 deficiency each significantly attenuated NETs and ferroptosis in CIAKI mice. Mechanistically, IL-33-enriched NETs suppressed IKKα expression, disrupted IKKα-β-catenin interaction, and impaired β-catenin nuclear translocation, thereby de-repressing long chain acyl CoA synthetase 4 transcription and amplifying ferroptotic injury. Restoration of IKKα stabilized β-catenin and attenuated NET-induced ferroptosis. Our study demonstrates that IL-33-enriched NETs promote renal tubular ferroptosis in CIAKI by suppressing IKKα and impairing β-catenin nuclear translocation. These findings identify the NETs-IL-33-IKKα-β-catenin pathway as a novel and therapeutically actionable mechanism underlying CIAKI, providing potential targets for its diagnosis and treatment.

PMID 42498057
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