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

Next generation sting agonist in combination with DNA methyltransferase inhibitors induce an apoptotic cell death mechanism driven by apoptosis in TP53-mutated Acute Myeloid Leukemia (ASH 2025) - "STING activation was also recently shown to trigger p53-independent apoptosis, andSTING agonists have shown a synergistic effect with BH3-mimetics in TP53-mutated AML cells.Here we studied the next-generation allosteric STING agonist C92 from Curadev Pharma, whichpotently binds and activates all human STING variants, in combination with the DNMTidecitabine (DAC) in TP53-mutated AML.MethodsTo test the hypothesis that DNMTis synergize with STING agonists, we treated AML cell lineswith wild-type (WT) (MOLM-14, OCI AML1) and mutated TP53 (KG1, KASUMI, U937) andpatient samples (N=5-10) with C92 in combination with decitabine (DAC)...To investigate apoptosis in TP53 KO vs WT, we measured Annexin Vlabeling by flow cytometry pre and post treatment with the 2 drugs, administered alone and incombination in the presence of the pan-caspase apoptosis inhibitor Z-VAD-FMK, the JAK/STATinhibitor ruxilitinib and the TBK1 inhibitor amlexanox...Finally, C92 and DAC combination decreased..."

Combination therapy • Epigenetic controller • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CXCL10 • CXCL11 • IFI27 • IFIH1 • IFIT2 • MX1 • OASL • STING • TNFA • TNFSF10

Therapeutic potential of IκB kinase epsilon inhibition in preventing meniscal degeneration of early osteoarthritis. (PubMed, Bone Joint Res) - "Furthermore, IKKε regulates meniscal degeneration through NF-κB signalling-mediated catabolism. Two IKKε/TBK1 inhibitors, amlexanox and BAY-985, are potential targets for the treatment of meniscal degeneration prior to OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • NFKBIA • RELA

Amlexanox Alleviates Renal Inflammation and Fibrosis by Inhibiting cGAS/STING/TBK1 and TGF-β1/Smad Signaling. (PubMed, Eur J Pharmacol) - "AMX exerts renoprotective effects by targeting both inflammation and fibrosis through the inhibition of the cGAS/STING/TBK1 and TGF-β1/Smad signaling pathway."

Journal • Fibrosis • Immunology • Inflammation • Renal Disease • CGAS • FN1 • STING • TGFB1

Combined treatment with amlexanox and cytarabine induces apoptosis via the S100A6-Akt pathway in KMT2A::AFF1-positive acute lymphoblastic leukemia. (PubMed, Leukemia) - No abstract available

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • AFF1 • KMT2A • S100A6

Targeting the cGAS-STING Pathway to Modulate Immune Inflammation in Diabetes and Cardiovascular Complications: Mechanisms and Therapeutic Insights. (PubMed, Curr Issues Mol Biol) - "Pharmacological inhibitors, including RU.521 (cGAS antagonist), C-176/H-151 (STING palmitoylation blockers), and the TBK1 inhibitor amlexanox, effectively lower pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and improve left ventricular ejection fraction in diabetic cardiomyopathy and ischemia-reperfusion injury models. Novel PROTAC degraders targeting cGAS/STING and natural products such as Astragaloside IV and Tanshinone IIA further support the pathway's druggability. Collectively, these findings position the cGAS-STING axis as a central molecular nexus linking metabolic derangement to cardiovascular pathology in T2DM and underscore its inhibition or targeted degradation as a promising dual cardiometabolic therapeutic strategy."

Journal • Review • Atherosclerosis • Cardiomyopathy • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • Reperfusion Injury • Targeted Protein Degradation • Type 2 Diabetes Mellitus • CGAS • IL1B • IL6 • NLRP3 • STING • TNFA

Amlexanox Ameliorates Traumatic Brain Injury by Restoring Autophagy-Lysosomal Function via cAMP Signaling Modulation. (PubMed, Int J Biol Sci) - "Behavioral assessments confirmed significant improvements in cognitive and neurological deficits following TBI. These findings establish that AMX is a promising therapeutic agent that restores lysosomal function and mitigates TBI-induced neuronal damage through multi-target PDE inhibition and anti-inflammatory actions."

Journal • CNS Disorders • Inflammation • Vascular Neurology

Combined amlexanox and anti-MCP-1 therapy suppresses tumor progression in a murine Lewis lung carcinoma model. (PubMed, Anticancer Drugs) - "Flow cytometric analysis indicated a significant decrease in M2 macrophages (F4/80+CD206+) in the intervention group, with no substantial change observed in the proportion of M1 macrophages (F4/80+CD86+). Combined administration of amlexanox and anti-MCP-1 mAb inhibited tumor cell proliferation, promoted apoptosis, and reduced infiltration of tumor-associated M2 macrophages, thereby contributing to suppression of tumor progression in the LLC murine model."

IO biomarker • Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • ARG1 • BCL2 • BCL2L1 • CCL2 • CD86 • MCL1 • MRC1 • TBK1

Development of translational read-through-inducing drugs as novel therapeutic options for patients with Fanconi anemia. (PubMed, Cell Death Discov) - "Amlexanox, an anti-inflammatory drug, also promotes read-through of premature stop codons caused by nonsense mutations. This study represents a milestone of drug development for FA as it paves the way for clinical development of TRIDs, indicating ataluren as a promising approach to address the genetic instability and reduce the risk of malignant transformation in FA cells. Moreover, these results highlight the importance of a reliable experimental pipeline to assess whether minimal protein rescue via translational read-through can yield meaningful phenotypic rescue."

Journal • Anemia • Hematological Disorders • Pediatrics • FANCA • FANCC • FANCF • LMNB1 • STAT2

Unlocking therapeutic potential of amlexanox in MASH with insights into bile acid metabolism and microbiome. (PubMed, NPJ Gut Liver) - "These findings uncover the multifaceted therapeutic potential of amlexanox in treating MASH and atherosclerosis by targeting bile acid metabolism, gut microbiota, hepatic inflammation, and fibrosis. Our study highlights amlexanox as a promising candidate for clinical applications."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Oncology • Solid Tumor

Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer. (PubMed, Cell Commun Signal) - "The IKBKE-inhibitor Amlexanox, clinically utilized for aphthous ulcers, as well as the MAPK8 inhibitor JNK-IN-8, reinstalled the DCIS-like phenotype of breast cancer cells on high matrix stiffness. This suggests that IKBKE and/or MAPK8 inhibitors could enhance the arsenal of treatments to prevent or treat breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • IKBKE • MAPK8

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