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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

PubMedJournal of agricultural and food chemistry2026-11-11

l-Arginine Ameliorates IBS-D by Modulating the Ligilactobacillus murinus-LCA-FXR/eNOS Signaling Axis.

Zheng Xianghou X, Ying Yitian Y, Yang Jing J, Liu Xia X et al.

l-Arginine is a semiessential amino acid with diverse metabolic functions and has been implicated in gastrointestinal health through interactions with the gut microbiota; however, its therapeutic potential in diarrhea-predominant irritable bowel syndrome (IBS-D) remains unclear. Here, an IBS-D mouse model was established in C57BL/6J mice, and multiomics analyses combined with in vivo and in vitro validation were performed to investigate the mechanisms underlying l-arginine-mediated protection. l-Arginine supplementation significantly alleviated IBS-D-like symptoms and improved intestinal barrier function. Transcriptomic analysis revealed the activation of the FXR/PI3K/AKT/eNOS signaling pathway, which was associated with enhanced nitric oxide production. Integrated metagenomic and transcriptomic analyses identified Ligilactobacillus murinus (L. murinus) as a key microbiota component associated with bile acid metabolism and eNOS expression. Furthermore, L. murinus transplantation reproduced the beneficial effects of l-arginine, and metabolomic analysis identified lithocholic acid (LCA) as a microbiota-derived metabolite involved in this process. In vitro experiments demonstrated that LCA alleviated lipopolysaccharide-induced epithelial inflammation and barrier dysfunction via FXR/eNOS activation. Collectively, these findings reveal that l-arginine ameliorates IBS-D through microbiota remodeling, LCA-mediated bile acid regulation, and activation of the colonic FXR/PI3K/AKT/eNOS axis, highlighting its potential as a microbiota-targeted therapeutic strategy.

PMID 43012686
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PubMedFrontiers in physiology2026-11-11

Differential effects of L-alanine, L-glutamine, L-arginine HCl, and glycine on feed intake and hypothalamic appetite-related responses in layer-type chicks.

Ghashghaei Elham E, Mijiyawa Ahmed A, Riaz Muhammad Faisal MF, Wang Minghui M et al.

While the effects of L-alanine, L-glutamine, L-arginine monohydrochloride (L-arginine HCl) and glycine on feed intake (FI) have been studied in chicks, their hypothalamic neuropeptide responses in layers remain unclear. Therefore, four trials were conducted to investigate the central effects of these amino acids on feed intake and hypothalamic neuropeptides in layer chicks. After intracerebroventricular administration, cumulative FI was measured over 2 hours and gene expression levels were determined using RT-PCR. Our results showed that L-alanine (1 µg and 2 µg) decreased FI at 120 minutes post-injection and was associated with decreased neuropeptide Y (NPY) mRNA expression (P < 0.05). L-glutamine (3 µg) increased FI at 60 minutes post-injection (P < 0.05), but had no significant effect on proopiomelanocortin (POMC), NPY, melanocortin receptor 4 (MC4R) or agouti-related peptide (AgRP) (P > 0.05). L-arginine HCl (1 µg) decreased FI at 120 minutes post-injection, while increasing POMC and MC4R expression, and decreasing NPY (P < 0.05). Glycine (3 µg) significantly reduced FI at all measured time intervals (P < 0.05). It had no impact on POMC expression (P > 0.05), but increased MC4R expression (P < 0.05) and reduced NPY expression more than AgRP expression, although neither was significantly decreased (P > 0.05). These results suggest that the effect of individual amino acids on FI and hypothalamic neuropeptide expression in layer chicks depends on the type and dose of amino acid. The present findings provide evidence of the acute central effects of amino acids in layer chicks.

PMID 43010951
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PubMedGut microbes2026-11-11

Human cognitive performance-associated gut microbiota influences learning and memory in mice through arginine and pterin metabolism.

Tracey Harry H, Antolín Anna A, Teichenne Joan J, Jones Oliver A H OAH et al.

The human gut microbiome undergoes changes across the lifespan and has been implicated in age-related decline. The symbol digit modalities test (SDMT) is a measure of information processing speed and is sensitive to mild cognitive impairment. Here, we assessed SDMT scores and fecal shotgun metagenomics in older individuals from the Imageomics cohort (n = 867) and performed fecal microbiota transplantation (FMT) from human donors to male C57BL/6 mouse recipients. In mice, we evaluated cognitive performance using the Morris water maze (MWM) and measured neurone density, fecal shotgun metagenomics, hippocampal metabolomics, and cortical gene expression to identify microbial-derived functional properties related to cognitive performance. In humans, both microbial species composition and functional profiles were associated with cognitive performance. FMT from high-SDMT donors improved cognitive performance and increased neuronal density in recipient mice compared with FMT from low-SDMT donors. In both humans and mice, higher cognitive performance was associated with arginine and proline metabolism and pterin-related pathways. In mice receiving microbiota from high-SDMT donors, cortical gene expression showed enrichment of dopamine receptor pathways and reduced dopamine reuptake and catecholamine biosynthesis. Our findings highlight the potential role of the gut microbiome in cognitive performance among older individuals, particularly information processing speed, and identify potential mechanisms involving alterations in arginine and pterin metabolism. Integrating human and mouse data supports a model in which microbiota-associated metabolic remodeling influences cognitive performance.

PMID 43010179
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PubMedNucleic acids research2026-11-11

Bipartite DNA-binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.

Lee Jisun J, Zhou Jujun J, Horton John R JR, Yu Meigen M et al.

B-cell leukemia/lymphoma 11B (BCL11B), despite its name, is a key regulator of T-cell development, lineage specification, and T-cell malignancies. BCL11B contains a bipartite DNA-binding domain composed of two C2H2 zinc finger arrays: low-affinity ZF2-3 and high-affinity ZF4-6. These arrays recognize similar six-nucleotide motifs, TG(n)CC(n), as seven of the eight DNA base-contacting residues are conserved between them. The most conserved interactions involve the central GG dinucleotides, recognized by arginine and lysine residues at the key base-interacting positions of ZF3 and ZF5. We determined eight crystal structures of ZF2-3 bound to 12- or 20-base pair DNA duplexes containing either one or two binding motifs. The structures reveal that ZF2-3 recognizes DNA with remarkable configurational flexibility, binding motifs on either the same or opposite DNA strands with variable spacing in three relative orientations: head-to-tail (or tail-to-head), head-to-head, and tail-to-tail. Analysis of BCL11B ChIP-seq peaks revealed a strong enrichment of 1-bp-spaced, same-orientation TGACC(c/t) motif pairs. We also examined six neurodevelopmental disorder-associated missense variants affecting DNA base-contacting residues. Substitutions that replace bulky, positively charged arginine or lysine with smaller or hydrophobic amino acids weaken DNA-binding affinity and specificity, whereas substitutions between asparagine and lysine alter base recognition preferences.

PMID 43010876
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PubMedRSC medicinal chemistry2026-11-11

Expanding the chemical space of guanidinium-stapled peptides with aromatic residues yields NCOA mimics with high affinity for nuclear receptors.

Trousselier Pauline P, Silvestri Aurora A, Peluso-Iltis Carole C, Osz Judit J et al.

Macrocyclization via guanidinium stapling is a modular synthetic approach to stabilize α-helical peptides and create constrained arginine mimics, while introducing positively charged, hydrogen-bonding moieties. To expand the structural diversity of guanidinium-stapled peptides, we incorporated non-natural amino acids, p-azidomethyl-l-phenylalanine (F*) and O-(2-azidoethyl)-l-tyrosine (Y*), to introduce aromatic groups into the macrocycle. We demonstrate compatibility with (i, i + 4) and (i, i + 7) stapling geometries and apply this approach to mimic nuclear receptor coactivator (NCOA) peptides for binding to human nuclear hormone receptors (NHR), including retinoic acid receptor alpha (RARα) and vitamin D receptor (VDR). Our structural and biophysical analyses reveal that aromatic elements within the guanidinium staple can modulate helical stability, enhance binding affinity, and contribute direct interactions with the protein surface.

PMID 43011727
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PubMedNature communications2026-11-11

The central coupler of ClpXP controls intersubunit communication and couples intrasubunit chemical energy with force generation.

Sosa Robert P RP, Florez Ariza Alfredo Jose AJ, Kim Jeonghoon J, Tong Alexander B AB et al.

ClpX is a clockwise hexameric helical arrangement that hydrolyzes ATP to unfold proteins and translocate them into the proteolytic chamber. We investigate the central coupler, a three α-helix module conserved among AAA+ ATPases, which is proposed to enable intersubunit communication and mechanochemical coupling. Although fundamental in AAA+ ATPases, the molecular mechanism underlying these processes remains elusive in ClpX. By combining single-molecule optical tweezers, biochemical assays and single-particle cryo-EM we demonstrate that the central coupler, of the second-highest subunit of the ClpX clockwise helical arrangement, positions its Arginine-finger, sensor-I and sensor-II to contact the ATP of the anticlockwise neighbor subunit to trigger its hydrolysis. Then, the central coupler of the highest subunit rapidly couples the ATP hydrolysis with the downward motion of its substrate-translocating loop, enabling fast force generation to swiftly unfold protein substrates while maximizing the thermodynamic efficiency of the motor.

PMID 43009491
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