ebselen (SPI-1005) / Sound Pharma - LARVOL DELTA

Sound Pharmaceuticals Receives FDA Breakthrough Therapy Designation for SPI-1005 to Treat Meniere’s Disease (Businesswire)

Breakthrough therapy • Otorhinolaryngology

Repurposing Ebselen for a potential blending-based therapeutic strategy against gastrointestinal nematodes of small ruminants. (PubMed, Res Vet Sci) - "The combination of Ebselen and IVM resulted in a statistically significant increase in larval migration inhibition, demonstrating a synergistic effect (>30 %). The data confirm the use of Ebselen and IVM in a novel blending-based therapeutic strategy to manage GIN that affects small ruminants."

Journal • Infectious Disease

Rescue of Aging-Dependent Reduction of Claudin-10b Expression by Glutamate in Mouse Intestinal MCE301 Cells. (PubMed, J Cell Biochem) - "Glu treatment stimulated Ca2+ influx, which was inhibited by BAPTA, a Ca2+ chelator, and ebselen, a voltage-dependent Ca2+ channel inhibitor...Glu reversed the Ten-1-induced reduction of CLDN10b mRNA and restored paracellular barrier function. These results suggest that Glu enhances the intestinal paracellular barrier function through the regulation of CLDN10b expression."

Journal • Preclinical • CLDN1 • TJP1

PRDX1 promotes testosterone synthesis and attenuates aging via redox regulation of ATG4B to modulate lipophagy. (PubMed, Nat Commun) - "Collectively, our findings demonstrate that PRDX1 promotes lipophagy and testosterone synthesis by regulating ATG4B. Our findings also propose the potential application of ebselen in the prevention and treatment of aging-related disorders, including late-onset hypogonadism."

Journal • Endocrine Disorders • Infertility • Sexual Disorders • ATG4B • PRDX1

Structure-Directed Optimization of Ebselen Derivatives as Potent NDM-1 Inhibitors Reverses Meropenem Resistance. (PubMed, J Med Chem) - "Mechanistically, 27k effectively inhibits the activity of NDM-1 by forming a Se-S covalent bond with the NDM-1 protein. Collectively, these findings confirm that compound 27k is an excellent NDM-1 covalent inhibitor, offering a promising lead compound for addressing bacterial resistance driven by NDM-1."

Journal

Ebselen Suppresses Breast Cancer Tumorigenesis by Inhibiting YTHDF1-Mediated c-Fos Expression. (PubMed, Int J Mol Sci) - "In addition, ebselen suppressed anchorage-independent growth in vitro and significantly reduced tumor growth in an orthotopic mouse model. These findings highlight YTHDF1 as a promising therapeutic target and support ebselen as a potential small-molecule inhibitor for breast cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • ANXA5 • FOS • YTHDF1

Atomistic modulation of MIF-2 structure, catalysis, and biological signaling via cysteine residues and a small molecule, Ebselen. (PubMed, Protein Sci) - "Our findings suggest that Ebselen partially disrupts the MIF-2 homotrimer, though the overall population of such a structure is <35%, even on the timescale of many hours. Ebselen does attenuate the biological functions of MIF-2, and solution structural biology captures the conformational transitions preceding the destabilized MIF-2 trimer."

Journal • DCT • MIF

Targeting neurotransmitter systems in bipolar disorder: a comprehensive review of novel pharmacological approaches (ECNP 2025) - "Adjunctive melatonin (2 mg modified-release with lithium plus risperidone) resulted in a superior YMRS reduction compared with placebo (mean difference –5.0; p<0.001)...In contrast, sole melatonin, levetiracetam plus quetiapine, celecoxib, ebselen, spironolactone and vitamin B₆ did not yield statistically significant YMRS improvements... Adjunctive melatonin, levetiracetam, palmitoylethanolamide and clonidine exhibit promising antimanic efficacy, and endoxifen is non-inferior to an established mood stabilizer. Heterogeneity in methodology and outcome measures precludes direct comparison. Larger, multicentre randomised trials with standardized endpoints and longer follow-up are warranted to corroborate these findings, evaluate durability of effect and inform personalized therapeutic strategies for acute mania and hypomania in bipolar disorder."

Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Sleep Disorder • NBN

Analysis of two screens reveals a correlation between antiamoebic and anti-tubulin activities of phenothiazine and triphenylethylene derivatives. (PubMed, RSC Med Chem) - "Furthermore, we identify potent MTAs such as ebselen and auranofin-both capable of crossing the blood-brain barrier-as promising candidates for repurposing. These findings demonstrate the value of MTA-based screening in anti-amoebic drug discovery and point toward new therapeutic avenues for treating this devastating disease."

Journal • CNS Disorders • Infectious Disease

SPI-1005 for the Treatment of Meniere's Disease (Open Label) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Sound Pharmaceuticals, Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Otorhinolaryngology

Therapeutic Potential of Se-N Heterocycles: Advances in Biological and Antioxidant Applications. (PubMed, Chem Asian J) - "Among them, ebselen (2-phenyl-1,2-benzoisoselenazol-3-[2H] one), a five-membered Se-N heterocyclic compound and its analogues have been extensively studied for their anti-inflammatory and neuroprotective roles...Recent advances underscore their potential in therapeutic applications including cancer, neurodegeneration, and ferroptosis. This review highlights the structural evolution and biological relevance of Se-N heterocycles as emerging enzyme mimetics and drug candidates for future therapeutics in diseases under oxidative stress."

Journal • Review • CNS Disorders • Oncology

Aminic Organoselenium Compounds: Promising Antioxidant Agents. (PubMed, ACS Omega) - "Key topics include the design principles of aminic organoselenium compounds, their performance relative to classical antioxidants like ebselen and α-tocopherol, and their promising use in developing treatments for conditions linked to oxidative stress. By consolidating advancements from the past two decades, this review connects existing research areas and suggests valuable pathways for future studies in developing multifunctional organoselenium antioxidants."

Journal • Review

Peroxisome Proliferator-Activated Receptor Family of Lipid-Activated Nuclear Receptors Alpha Silencing Promotes Oxidative Stress and Hypertrophic Phenotype in Rat Cardiac Cells. (PubMed, Antioxidants (Basel)) - "This study aimed to investigate the PPARα role in hypertrophic phenotype and to evaluate the potential effects of the antioxidant Ebselen (Ebs) treatment on changes associated with PPARα depletion...Treatment with Ebs, a redox-active compound with inhibitory effects on ferroptosis and epigenetics, reversed hypertrophic phenotype and restored miRNA levels. In conclusion, we found that PPARα depletion promotes oxidative stress and hypertrophic phenotype and that Ebs may act as a potential therapeutic agent."

Journal • Preclinical • Metabolic Disorders • FBXO32 • MIR132 • MIR331 • MIR34A • PPARA

Polymer-engineered liposome-delivered Ebselen against tumor through GSH/H2O2-responsive disruption of redox homeostasis and direct p53 activation. (PubMed, Biomaterials) - "In vivo experiments demonstrated that EbSe@LNP regulates immune cell ratios in tumor and spleen, effectively combating cancer progression. Collectively, this study not only offers a nano-delivery strategy to overcome the poor aqueous solubility of EbSe, but also elucidates its underlying antitumor mechanisms, offering a strong scientific foundation for its clinical translation."

Journal • Metabolic Disorders • Oncology • ITGA4

Construction of a prognostic risk model for acute myeloid leukemia based on exosomal genes and analysis of immune microenvironment characteristics. (PubMed, Sci Rep) - "Molecular docking studies confirmed strong binding affinity of verteporfin (ITGA4 inhibitor, docking score=-16.0 kcal/mol) and ebselen (MPO inhibitor) to their respective targets, suggesting potential therapeutic strategies to overcome chemotherapy resistance. This study establishes a robust 13-gene exosome-based prognostic signature for AML risk stratification and identifies novel immunomodulatory mechanisms mediated by exosome-driven Treg polarization."

Biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CANX • HLA-DRA • ITGA4 • MYL6 • PSMA2 • TP53

Thiazole- and Benzothiazole-Based Organoselenium Compounds as Dual-Action Agents: Tyrosinase Inhibitors and Functional Mimics of Glutathione Peroxidase. (PubMed, Inorg Chem) - "Selones 1 and 3 demonstrated superior glutathione peroxidase-like catalytic and radical scavenging activity, exhibiting up to 2-fold greater efficacy than the well-known antioxidant ebselen. Notably, selone 3 effectively suppressed enzymatic browning in clarified banana and apple juices, suggesting dual utility in redox regulation and food preservation. These results provide valuable insights into the design of chalcogen-based tyrosinase inhibitors."

Journal • Tyrosinase

SPI-1005 for the Treatment of Meniere's Disease (Open Label) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Sound Pharmaceuticals, Incorporated | Trial completion date: Oct 2026 ➔ Feb 2027 | Initiation date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Oct 2026 ➔ Feb 2027

Trial completion date • Trial initiation date • Trial primary completion date • Otorhinolaryngology

SPI-1005 in Adults Receiving Cochlear Implant (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Sound Pharmaceuticals, Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Mood Disorders • Otorhinolaryngology

Synthetic and semi-synthetic antioxidants in medicine and food industry: a review. (PubMed, Front Pharmacol) - "Nevertheless, some compounds, such as ebselen, edaravone, MitoQ10, and potentially N-acetylcysteine, have shown promising results...One emerging therapeutic strategy involves inhibition of NADPH oxidase (NOX) enzymatic activity, with compounds such as ebselen, S17834, and GKT137831 showing potential across various disease models...Despite extensive research, only a few synthetic antioxidants, such as edaravone, are currently used in clinical practice. Currently, no new antioxidant drugs are expected to receive regulatory approval in the near future."

Journal • Review

Carboxymethyl chitosan and poly-γ-glutamic acid-based gastroretentive sponge with high swelling and mechanical stability for targeted eradication of Helicobacter pylori. (PubMed, Carbohydr Polym) - "Loaded with amoxicillin and ebselen, the CPP sponge significantly enhanced drug bioavailability and achieved a 98.59 % bacteriostasis ratio against H. pylori in a mouse model. The CPP sponge's triple-network structure, combining intramolecular amide bonds, intermolecular amide bonds, and hydrogen bonds, provided excellent mechanical stability and swelling properties. This study highlights the potential of the CPP sponge as an effective therapeutic platform for H. pylori infection, offering sustained drug release, improved gastric retention, and enhanced therapeutic efficacy."

Journal • Gastric Cancer • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Oncology • Peptic Ulcer • Solid Tumor

Inhibitor-Dependent Tolerance of New Delhi Metallo-β-Lactamase Driven by Single Mutation-Induced Conformational Changes. (PubMed, J Am Chem Soc) - "We employ hydrogen/deuterium exchange mass spectrometry (HDX-MS) to map conformational landscapes of NDM in the ligand-free state and in the bound states with inhibitors l-captopril, d-captopril, ebselen, and aspergillomarasmine A (AMA), respectively. Overall, this work unveils a novel perspective─resistance mutations function not merely as chemical optimizers but as allosteric modulators that exploit inherent protein plasticity. These insights position the α3-L8 region as a compelling target for developing novel inhibitors, providing a blueprint for combating the next frontier of antimicrobial resistance."

Journal

Synthesis and Biological Activity of Benzoselenazole and Benzo[b]Selenophene Analogues: A Review. (PubMed, Drug Dev Res) - "Among selenium-containing compounds, ebselen is the most extensively studied drug candidate...Consequently, selenium-containing heterocyclic compounds represent a promising avenue for drug discovery and development. This review summarizes three synthetic approaches for constructing selenium-containing heterocyclic compounds and emphasizes their notable biological activities and potential applications in pharmaceuticals."

Journal • Review • Oncology

Small molecule selenium-based Glutathione Peroxidase 4 mimetic inhibits lipid peroxidation and protects cultured neurons from ferroptosis. (PubMed, Free Radic Biol Med) - "Thus, Compd. 5, a synthetic selenium-based small molecule with specific GPX4-like activity, represents a new class of anti-ferroptotic agents with significant translational potential for the treatment of neurodegenerative and other ferroptosis-driven diseases."

Journal • CNS Disorders • GPX1 • GPX4

Ebselen inhibited H3N2 influenza virus-induced apoptosis through the mitochondria-mediated signaling pathway. (PubMed, Free Radic Biol Med) - "Further investigation revealed that ebselen inhibits mitochondria-mediated apoptosis, thereby preventing H3N2-mediated apoptosis. In summary, this study suggests that ebselen has potential as anti-H3N2 influenza virus drug."

Journal • Cardiovascular • Infectious Disease • Influenza • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

Magnetic resonance spectroscopy biomarkers of anti-inflammatory interventions in mood disorders: A systematic review of clinical trials. (PubMed, J Affect Disord) - "Anti-inflammatory agents induce MRS-detectable neurochemical changes in mood disorders. These shifts may relate to symptom improvement. Further research is needed to elucidate the mechanisms underlying these effects."

Biomarker • Journal • Bipolar Disorder • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mood Disorders • Psychiatry