Aphthasol (amlexanox) / Abeona Therap, Esteve - LARVOL DELTA

Amlexanox inhibits production of type I interferon and suppresses B cell differentiation in vitro: a possible therapeutic option for systemic lupus erythematosus and other systemic inflammatory diseases. (PubMed, RMD Open) - "Our findings demonstrate inhibitory effects of amlexanox on type I IFN production and B cell differentiation in primary human cells. Inhibition of TBK1 could potentially be a therapeutic option for the treatment of type I IFN-driven systemic inflammatory diseases."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Scleroderma • Sjogren's Syndrome • Systemic Lupus Erythematosus • Systemic Sclerosis • CD40LG • IL21 • MX1 • TBK1

Condensation of cellular prion protein promotes renal fibrosis through the TBK1-IRF3 signaling axis. (PubMed, Sci Transl Med) - "Treating mice with amlexanox, a US Food and Drug Administration-approved inhibitor of TBK1, either before the onset of renal fibrosis (in UUO and UIRI models) or after its establishment (in adenine- and aristolochic acid-induced CKD models), mitigated worsening of renal fibrosis and renal function. Collectively, our findings uncovered a mechanism involving phase separation of PrPC underlying renal fibrosis and support further study of the PrPC-TBK1-IRF3 axis as a potential therapeutic target for CKD."

Journal • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • PRNP • SMAD4 • TGFB1

Distinct pathogenic mutations in ARF1 allow dissection of its dual role in cGAS-STING signalling. (PubMed, EMBO Rep) - "Treatment of patient fibroblasts in vitro with the STING signalling inhibitors H-151 and amlexanox reduces chronic interferon signalling. Summarizing, our data reveal the molecular basis of a ARF1-associated type I interferonopathy allowing dissection of the two roles of ARF1, and suggest that pharmacological targeting of STING may alleviate ARF1-associated auto-inflammation."

Journal • Inflammation • Interferonopathies • ARF1

Amlexanox ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting Th17 cells and the NF-κB signal pathway. (PubMed, Biomed Pharmacother) - "These findings indicated that amlexanox effectively alleviated psoriatic symptoms through both oral and topical administration. We propose that amlexanox is a potent therapeutic candidate for the treatment of psoriasis."

Journal • Dermatitis • Dermatology • Immunology • Psoriasis • IL17A

MULTI-BIOINFORMATICS REVEALED DRUGGABLE PROTEIN NETWORK OF PROGRESSION FROM GASTRIC INTESTINAL METAPLASIA TO GASTRIC ADENOCARCINOMA (UEGW 2024) - "Computational drug repurposing of approved and investigational drugs/compounds (e.g., as found on www.clinicaltrials.gov) identified the following drugs as effective for GIM: dasatinib with or without erlotinib, nilotinib, afatinib on SRC, SM1-71 on SRC, JNJ-26483327 on EGFR, Afatinib on EGFR, ingenol mebutate on protein kinase C (PKC) family, amoxapine, benoxaprofen, avobenzone, amlexanox, alprazolam, praziquantel, ibuprofen piconol, tranilast, and restoril. The druggable protein network associated with GIM progression toward GA was identified. The distinct phenotypic patterns between GIM and GA might challenge the notion that GIM serves as the primary precancerous lesion in GA tumorigenesis rather than shares a common cause with tissue-resident stem cells. Further validation of the druggable protein network is needed for the development of a cost-effective surveillance program and preventive treatment of the GIM-to-GA progression."

IO biomarker • Breast Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRCA1 • CD44 • CTNNB1 • EGFR • JUN • RBP2 • SRC

Amlexanox reduces new-onset atrial fibrillation risk in sepsis by downregulating S100A12: a Mendelian randomization study. (PubMed, Front Cardiovasc Med) - "Targeting S100A12 identifies five potential small molecule therapeutics: amlexanox, balsalazide, methandriol, olopatadine, and tiboloe. We identified S100A12 as a key gene influencing the new-onset AF in sepsis through immune regulation, presenting considerable diagnostic and predictive value. Notably, amlexanox, by targeting S100A12 emerges as the most clinical relevant intervention for managing new-onset AF in sepsis patients."

Journal • Atrial Fibrillation • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • IL1B • IL6 • S100A12 • TNFA

Short-Term Systemic Pre-Treatment with Amlexanox, a TBK1/IKKe Inhibitor, Prevents Intimal Hyperplasia and Promotes Re-Endothelialization Following Balloon Angioplasty (ACS-CLINCON 2024) - "This is the first report showing that 1-day pre-treatment with Amlexanox significantly reduces IH and promotes re-endothelialization following carotid balloon angioplasty in a rat model, supporting future translational applications of systemic or balloon/stent incorporated Amlexanox in acute endovascular interventions to prevent post-angioplasty restenosis."

Cardiovascular • Peripheral Arterial Disease • CD31 • IFNG • PECAM1

TBK1 is involved in M-CSF-induced macrophage polarization through mediating the IRF5/IRF4 axis. (PubMed, FEBS J) - "Mechanistically, TBK1 deletion or inhibition by amlexanox or GSK8612 reduced the expression of the transcription factor interferon-regulatory factor (IRF)4 and increased the level of IRF5 activation in macrophages stimulated with M-CSF, leading to an M1-like profile with highly proinflammatory factors. IRF5 deletion reversed the effect of TBK1 inhibition on M-CSF-mediated macrophage polarization. Our findings suggest that TBK1 contributes to the regulation of macrophage polarization in response to M-CSF stimulation partly through the IRF5/IRF4 axis."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • ARG1 • CD86 • CSF1 • IL1B • IRF4 • IRF5 • TBK1 • TNFA

Amlexanox Enforces Osteogenic Differentiation and Bone Homeostasis Through Inhibiting Ubiquitin-Dependent Degradation of β-Catenin. (PubMed, Int J Biol Sci) - "Importantly, AM stimulated osteogenesis in human BMSCs. By promoting osteogenesis at the expense of adipogenesis and hindering osteoclastogenesis, AM offers a promising therapeutic strategy for osteoporosis due to its established safety profile."

Journal • Osteoporosis • Rheumatology • Targeted Protein Degradation • CTNNB1 • TNFSF11

Protein Kinases in Obesity, and the Kinase-Targeted Therapy. (PubMed, Adv Exp Med Biol) - "Nifedipine, calcium channel blocker, stimulates lipogenesis and adipogenesis by downregulating AMPK and upregulating mTOR, which thereby enhances lipid storage. Co-treatment of antiobesity and antidiabetic herbal compound, berberine with antipsychotic drug olanzapine decreases the accumulation of triglyceride. While low-dose rapamycin, metformin, amlexanox, thiazolidinediones, and saroglitazar protect against insulin resistance, glucagon-like peptide-1 analog liraglutide inhibits palmitate-induced inflammation by suppressing mTOR complex 1 (mTORC1) activity and protects against lipotoxicity."

Journal • Review • CNS Disorders • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • ATF4 • ATF6 • MAPK8 • PRKCB • TCF4

Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease. (PubMed, Clin Exp Immunol) - "In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD."

Immune cell • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • IFNA1 • IL10 • IL1B • IL6 • TBK1 • TGFB1 • TNFA

Targeting TANK-binding kinase 1 attenuates painful diabetic neuropathy via inhibiting microglia pyroptosis. (PubMed, Cell Commun Signal) - "Our findings revealed a novel causal role of TBK1 in pathogenesis of PDN, which raises the possibility of applying amlexanox to selectively target TBK1 as a potential therapeutic strategy for PDN."

Journal • Diabetes • Diabetic Neuropathy • Inflammation • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus • NLRP3

A Comparative Evaluation of Clinical Efficacy of Topical Amlexanox and Triamcinolone Acetonide in Oral Lichen Planus. (PubMed, Cureus) - "Given its anti-inflammatory properties and lower incidence of adverse effects relative to corticosteroids, amlexanox acts as a promising first-line therapeutic option for OLP. In cases of inadequate response, adjunctive therapies can be considered."

Journal • Dermatology • Dermatopathology • Immunology • Lichen Planus • CD8 • TNFA

Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1. (PubMed, Sci Rep) - "The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A...MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease."

Journal • Inflammation • MRTFA

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure. (PubMed, Neurotherapeutics) - "Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management."

Journal • CNS Disorders • Epilepsy • Inflammation

Efficacy of Aloe Vera, Amlexanox (5%), and Triamcinolone Acetonide (0.1%) in the Management of Oral Lichen Planus. (PubMed, J Pharm Bioallied Sci) - "There was a statistically considerable decrease in the VAS pain scale score, reduction in the erosive area on buccal mucosa, and healing of ulcer from day 1st to 15th day with all three tested drugs. All drugs used in this study; aloe vera, triamcinolone acetonide, and amlexanox were effective in treating OLP patients."

Journal • Dermatology • Dermatopathology • Lichen Planus • Pain

Efficacy of Clobetasol Propionate (0.05%), Amlexanox (5%), and Triamcinolone Acetonide (0.1%) in the Treatment of Oral Lichen Planus. (PubMed, J Pharm Bioallied Sci) - "A total of 120 patients diagnosed with oral lichen planus were equally divided into three groups and treated with 0.05% clobetasol propionate (group A), 0.1% triamcinolone acetonide (group B), and 5% amlexanox (group C) topical medicaments. Triamcinolone acetonide (0.1%) was effective in reducing the erosive lesions on buccal mucosa when compared with 0.05% clobetasol propionate and 5% amlexanox. Clobetasol propionate, triamcinolone acetonide, and amlexanox were effective in treating OLP patients."

Journal • Dermatology • Dermatopathology • Lichen Planus • Pain

Evaluation of the Effectiveness of Amlexanox in the Treatment of Erosive Oral Lichen Planus: A Clinical Experience from a Tertiary Care Center. (PubMed, J Int Soc Prev Community Dent) - "Amlexanox provides an earlier onset of pain relief in the treatment of EOLP, whereas providing a comparable reduction in the erosive area compared with triamcinolone. Topical amlexanox appears to be as effective as triamcinolone and is a promising alternative in the management of the erosive lichen planus with minimal adverse effects."

Journal • Dermatology • Dermatopathology • Lichen Planus • Pain

TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro. (PubMed, BMC Med) - "Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • CD68 • PTPRN • TARDBP • TNFSF12 • TNFSF13

Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment. (PubMed, ACS Nano) - "These findings suggested that VAPN had potential to modulate the immune microenvironments of adipose tissues for the immunologic treatment of obesity. Although we used amlexanox as a model drug and anti-VCAM-1 antibody in VAPN, the concept of immune nanomodulators can be widely applied to the immunological treatment of obesity."

Journal • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • VCAM1

Ubiquitin specific protease 38 aggravates pathological cardiac remodeling by stabilizing phospho-TBK1. (PubMed, Int J Biol Sci) - "The TBK1 inhibitor Amlexanox significantly alleviates pressure overload induced-cardiac hypertrophy and myocardial fibrosis in mice with USP38 overexpression. Our results demonstrate that USP38 serves as a positive regulator of pathological cardiac remodeling and suggest that targeting the USP38-TBK1 axis is a promising treatment strategy for hypertrophic heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Targeted Protein Degradation • TBK1

Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC. (PubMed, Adv Sci (Weinh)) - "Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib-resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1-mediated pS417-AGO2 and suggest potential therapeutic approaches for NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF-κB and STAT3 signaling pathways. (PubMed, Sci Rep) - "In addition, the combination of amlexanox and SPI (a STAT3 selective inhibitor) showed high efficiency in inhibiting the production of neurotoxic and pro-inflammatory mediators. Overall, our data provide rational insights into the mechanisms of amlexanox as a potential therapeutic strategy for neuroinflammation-related diseases."

Journal • Allergic Rhinitis • Asthma • CNS Disorders • Diabetes • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Pulmonary Disease • Respiratory Diseases • Type 2 Diabetes Mellitus

Amlexanox for Type 2 Diabetes and Obesity (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: University of Michigan | N=15 ➔ 7 | Suspended ➔ Terminated; Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.

Clinical protocol • Enrollment change • Trial termination • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

COMPARATIVE EFFICACY OF THERAPEUTIC INTERVENTIONS FOR THE MANAGEMENT OF RECURRENT APHTHOUS ULCERS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS. (PubMed, J Evid Based Dent Pract) - "Our NMA has identified several interventions to be more effective than a placebo. Laser therapy may be an option for promoting pain management, however, most have only been tested in 1 or 2 trials. Further studies with rigorous methodology on larger samples are recommended to strengthen the current evidence."

Journal • Retrospective data • Review • Pain