Actavis · PTGS1 · Small Molecule
diclofenac is a small molecule developed by Actavis. It is approved for therapeutic indications via transdermal.
| Brand Names | Oxa Gel, diclofenac, topical |
| Company | Actavis |
| Drug Class | Small Molecule |
| Molecular Target | PTGS1, PTGS2 |
| Route | Transdermal |
| Status | Approved |
diclofenac acts on 2 molecular targets:
| PTGS1 | prostaglandin-endoperoxide synthase 1 (COX3, PCOX1) |
| PTGS2 | prostaglandin-endoperoxide synthase 2 (GRIPGHS, hCox-2) |
diclofenac is developed for 5 unique indications across 3 therapeutic areas.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Musculoskeletal and connective tissue disorders | Musculoskeletal pain | ✓ Approved |
| Musculoskeletal and connective tissue disorders | Myositis | ✓ Approved |
| Musculoskeletal and connective tissue disorders | Rheumatoid arthritis | ✓ Approved |
| Injury, poisoning and procedural complications | Traumatic shock | ✓ Approved |
| Skin and subcutaneous tissue disorders | Actinic keratosis | Phase III |
Ma Xiang X, Shan Qingqing Q
Alnezary Faris S FS, Almutairi Masaad Saeed MS
The escalating prevalence of multidrug-resistant skin and soft tissue infections (SSTIs) undermines current decolonization strategies. While mupirocin remains the gold standard for MRSA, its inactivity against Pseudomonas aeruginosa creates a critical therapeutic gap in polymicrobial wounds. The development of effective alternatives is currently impeded by in vitro assays that fail to mimic the physical barriers of the wound microenvironment. To address these challenges, this study aimed to validate a comprehensive multi-tiered screening platform and evaluate the efficacy of a novel 5% ceftriaxone gel as a broad-spectrum alternative. We established a comprehensive, multi-tiered validation platform to assess a novel 5% ceftriaxone gel formulation. The pipeline included: (1) Agar Well Diffusion to quantify vehicle release kinetics; (2) a Gauze-Disk Biofilm Prevention assay to evaluate penetration through standard dressings; (3) an Ex Vivo Porcine Ear Skin model to challenge efficacy against the stratum corneum and wound lipids; and (4) an In Vivo Galleria mellonella model to assess the prevention of systemic lethality. The formulation was benchmarked against mupirocin, and triple antibiotic ointment. In diffusion assays, the 5% ceftriaxone gel exhibited broad-spectrum release, producing inhibition zones > 44 mm against staphylococci and a mean zone of 50.1 mm against P. aeruginosa. In the Gauze model, the formulation successfully permeated standard cotton dressings, achieving complete bacterial eradication (No Growth) across all tested strains, including P. aeruginosa, significantly outperforming positive controls (p < 0.001). Crucially, in the ex vivo porcine model, the gel maintained potent bioactivity despite the lipid barrier, yielding significant > log reductions at 24 h across all strains: MRSA (> 2.5-log), MSSA (> 3-log), S. pyogenes (> 4-log), and P. aeruginosa (> 4-log). Furthermore, topical application in the in vivo G. mellonella model significantly reduced the systemic bacterial burden across all pathogens (p < 0.05), validating trans-cuticular protective efficacy. This study evaluates a robust, ethical preclinical screening platform for topical antimicrobials. The findings suggest that a high-concentration ceftriaxone gel has the potential to address the "mupirocin gap" by providing broad-spectrum coverage against both resistant staphylococci and Pseudomonas in experimental models.
Cutrona Marley M, Golant Alexandra K AK
Residual disease is relatively common in dupilumab-treated patients with atopic dermatitis (AD). Adjunctive topical treatment, including topical corticosteroids or non-steroidal treatments, are often needed. In this study, we evaluated the clinical characteristics and outcomes of patients with AD on dupilumab with residual disease who were subsequently treated with roflumilast cream. This was a retrospective chart review conducted at a single academic center. Electronic medical records were searched to identify patients with AD who were prescribed dupilumab and were subsequently prescribed roflumilast cream for persistent or residual disease between July 2022 and January 2026. Of the 676 cases of AD identified and included in this review, there were 30 cases of dupilumab-treated patients with residual AD disease. One additional patient with de novo facial erythema on dupilumab was described qualitatively. Following roflumilast cream treatment, physician-documented clinical improvement was reported in 83% (25/30) of these patients. Of 18 patients with patient-reported outcomes, ten reported improvement with roflumilast cream (including resolution of disease, near resolution, or significant improvement with decreased flares); five reported reduced pruritus (1 with fully resolved itch); three reported no improvement; and one discontinued roflumilast cream due to burning. No additional adverse events were documented in the medical records. In this retrospective case series, adjunctive roflumilast cream was associated with physician-documented clinical improvement in most dupilumab-treated patients with residual AD.
Zhang Bihang B, Saito Natsumi N, Wu Yunyan Y, Shirado Takako T et al.
Epithelial cell-based approaches - including cultured keratinocyte sheets, bilayered skin substitutes, and cell-enriched wound dressings derived from epidermal cells - have been explored to enhance wound epithelialization; however, most studies have focused on epidermis-derived cells. Wound-healing potential of epithelial cells originating from different regions of human hair follicle remains insufficiently characterized. Epithelial cells were isolated from distinct regions of human scalp hair follicles, including upper root epithelial cells (UECs), lower root epithelial cells (LECs), and bulb epithelial cells (BECs), and were compared with epidermal keratinocytes. Cell viability, proliferation, and phenotypic characteristics were evaluated in vitro. In vivo epithelialization was assessed using a full-thickness wound model in immunodeficient mice following topical application of each cell population. Histological analyses were performed on healed tissue, and donor-site outcomes were explored using a rat whisker model. BECs exhibited the highest viability and proliferative capacity, along with a lower proportion of differentiated keratinocytes. All cell-treated groups enhanced epithelialization compared to controls, with BECs-treated wounds showing the most pronounced improvement. Histological analysis demonstrated reduced scar formation and increased retention of human-derived cells in regenerated epidermis following BECs treatment. In rat model, hair follicle regeneration was observed after bulb removal, although regenerated whiskers exhibited reduced thickness and length. These findings provide proof-of-concept evidence that epithelial cells derived from the human hair follicle bulb possess favorable biological properties and enhance epithelialization in preclinical wound model. Hair follicle-derived epithelial cells may represent promising cell source for cutaneous regeneration, although further investigation is required to establish clinical applicability.
Yang Yunhong Y, Guo Lihua L, Yang Yunsong Y, Tang Han H et al.
This study comprised two complementary levels of investigation. First, we characterized the global burden, temporal trends, and socioeconomic inequalities of dermatitis as an aggregated disease category. Second, within this broader public-health context, we investigated whether moxibustion and topical capsaicin alleviate pruritus and inflammatory skin damage in a rat model of atopic dermatitis (AD) and explored their potential convergent regulation of the Janus kinase (JAK)/STAT signaling pathway. The study comprised a population-level contextual analysis and a disease-specific experimental investigation. Age-standardized incidence rates (ASIRs) and disability-adjusted life years (DALYs) attributable to each risk factor for dermatitis were extracted and assessed from the Global Burden of Disease (GBD) database. The GBD component was used to characterize the broader public-health burden of dermatitis and was not interpreted as an AD-specific epidemiological analysis. An AD rat model was established using 2,4-dinitrochlorobenzene (DNCB) in an acetone solution. Successfully modeled rats were randomly assigned to untreated model, mometasone furoate cream, moxibustion, or topical capsaicin groups. The standard pharmacological treatment group was included as a therapeutic efficacy benchmark, whereas capsaicin was used as a sensory-neuron-modulating active comparator for the exploratory analysis of downstream molecular convergence. Proteomic analysis was used to identify treatment-associated pathways, and changes in IFN-γ/JAK1/STAT1/STAT3 signaling components were subsequently assessed by western blotting, RT-qPCR, and immunohistochemistry. In addition to skin-lesion severity and scratching behavior, pruritus-related neuroimmune mediators were evaluated. Serum IL-31 concentrations were measured by ELISA. Cutaneous IL-31 and TRPV1 expression was assessed by immunohistochemistry, and substance P immunoreactivity was evaluated by immunofluorescence. The relative mRNA expression of Trpv1, SP(Tac1), and CGRP in lesional skin was measured by RT-qPCR. The global incidence of dermatitis increased, with a higher burden in females. Significant inequalities in incidence and DALYs existed across countries of varying sociodemographic index (SDI) levels. At the experimental level, target intersection analysis identified 302 genes shared by capsaicin, AD, and pruritus, while lesional-skin proteomics identified 257 common differentially expressed proteins. Exploratory proteomic enrichment identified JAK/STAT signaling as the most prominent candidate pathway in the enrichment bubble plot. AD model rats exhibited increased scratching, upregulated pruritus-related mediators (IL-31, TRPV1, substance P, and Trpv1/Tac1/CGRP transcripts), exacerbated skin lesions, histopathological damage, and a pro-inflammatory shift (elevated IL-1, IL-4, IL-6, TNF-α, IFN-γ; reduced IL-10). Mometasone furoate predictably alleviated these AD-like manifestations. Both moxibustion and capsaicin treatments reversed these trends, improving pathology, restoring spleen/thymus indices, and downregulating IFN-γ expression and JAK1/STAT1/STAT3 phosphorylation. Aggregated dermatitis continues to impose a substantial and unevenly distributed global health burden. Within this broader public-health context, the experimental findings indicate that moxibustion and topical capsaicin alleviate pruritus and inflammatory skin damage in rats with AD. These improvements were accompanied by attenuation of IFN-γ/JAK1/STAT1/STAT3-associated signaling, supporting the potential involvement of the JAK/STAT pathway in the observed treatment responses.
Pires L L, Calcada C C, Cerqueira-Rodrigues B B, Fan Y Y et al.
Melanoma is highly aggressive with limited options in advanced disease. Photodynamic therapy (PDT) has shown poor efficacy in pigmented melanoma due to restricted light penetration and intrinsic ROS resistance. A novel approach is investigated here. Full-thickness (4 mm) S91 pigmented melanoma grown intradermally in syngeneic immunocompetent (DBA) mice was treated using dual photosensitizers targeting tumor cells and microvasculature, together with a topical optical clearing agent. Anti-tumor immune effects were investigated in multiple functional assays, and the mechanisms-of-action were explored. Primary tumor was eradicated in all mice, with 95% disease-free survival at 90 d, falling to 20% upon CD8 + T-cell depletion pre-treatment. The median survival in nude mice was 21 d. Treated DBA mice also rejected systemic tumor re-challenge at 30 d post treatment. There was delayed growth of untreated contralateral tumors and of tumors co-injected into naïve mice together with splenocytes from treated mice. Biomarker analysis showed rapid tumor infiltration by CD8+ and CD3+ T cells, reduced suppressive myeloid populations, and widespread immune activation. Gene expression profiling revealed enrichment of immune-related pathways and long-lasting memory. Photodynamic immune stimulation treatment can destroy primary pigmented melanoma far beyond the depth of light penetration and has potent anti-tumor systemic efficacy.
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