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

Investigation of chalcogen bonding in ebselen·DMAP co-crystals using synchrotron far-infrared spectroscopy. (PubMed, Phys Chem Chem Phys) - "The Se⋯N chalcogen bond vibrational frequency and infrared band profile is system specific, however, and there is no correlation observed between the frequency and chalcogen bond strength. Ultimately, this work represents, to our knowledge, one of the first uses of far-infrared spectroscopy to identify chalcogen bonding interactions in solid-state crystalline systems."

Journal

SPI-1005 Improves Low-to-mid Frequency Hearing in Meniere's Patients That Supports Treating Sudden Sensorineural Hearing Loss (AAO-HNSF 2026) - "MD patients treated with oral SPI-1005 showed clinically relevant and statistically significant improvements in low-to-mid frequency hearing and speech discrimination during RCT/OLE. The durability of response over 3–15-months of follow-up supports future testing of SPI-1005 in SSNHL."

Clinical • Otorhinolaryngology • GPX1

SPI-1005 Improves Low-to-mid Frequency Hearing in Meniere's Patients That Supports Treating Sudden Sensorineural Hearing Loss (AAO-HNSF 2026) - "MD patients treated with oral SPI-1005 showed clinically relevant and statistically significant improvements in low-to-mid frequency hearing and speech discrimination during RCT/OLE. The durability of response over 3–15-months of follow-up supports future testing of SPI-1005 in SSNHL."

Clinical • Otorhinolaryngology • GPX1

Organoselenium compounds as redox modulators of inflammation: Synthetic strategies, mechanistic insights, and therapeutic potential. (PubMed, Bioorg Chem) - "The chemical versatility of selenium enables its incorporation into diverse scaffolds, offering - in some cases - a rewarding strategy to achieve enhanced pharmacological profiles, improved bioavailability, and reduced toxicity compared to classical anti-inflammatory agents. This review covers recent advances in the design, synthesis, and biological evaluation of selenium-based small molecules with anti-inflammatory properties, highlighting their potential as next-generation therapeutic agents."

Journal • Review • Cardiovascular • CNS Disorders • Immunology • Inflammation • Rheumatology • PTGS2

Ebselen sensitizes multidrug-resistant cancer cells to doxorubicin by disrupting cellular redox homeostasis and inducing ferroptosis. (PubMed, Life Sci) - "Ebselen sensitizes MDR cancer cells to doxorubicin by targeting the TrxR-NRF2/Keap1 axis, disrupting redox homeostasis, inducing iron-dependent ferroptosis and suppressing drug efflux. These findings identify TrxR as a promising therapeutic target for overcoming chemoresistance."

Journal • Oncology • ABCB1 • ACO1 • GPX4 • NQO1 • TFRC

Vancomycin rescues sensitivity to isoniazid in clinical isolates of drug-resistant Mycobacterium tuberculosis. (PubMed, Microbiol Spectr) - "Our previous work with lab-evolved isoniazid-resistant Msmeg showed that resistant bacteria have a diminished capacity to counter oxidative stress, causing them to be sensitive to several drugs like ebselen, phenylarsine oxide, vancomycin, all of which are known to affect redox homeostasis in mycobacteria. Since isoniazid is a primary TB drug, and vancomycin is already in clinical use for the treatment of common bacterial infections, they can easily be introduced as a combination into the pipeline for TB treatment. Our work addresses the urgent need for newer TB treatment strategies and provides data indicating the potential for a clinical trial in MDR TB cases."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A novel ring-opened ebselen scaffold with potent anti-angiogenic activity against cancer: synthesis, biological evaluation, and molecular docking. (PubMed, Bioorg Med Chem) - "At 6.25 μM, 3d significantly inhibited angiogenesis in transgenic zebrafish, reducing subintestinal vessel area by 25.6% (p < 0.001) and intersegmental vessel number by 15.8% (p < 0.01), suggesting a potential anti-angiogenic activity against cancer. Docking and MD simulations suggested a possible interaction of 3d to MetAP2."

Journal • Lung Cancer • Oncology • Solid Tumor • METAP2

Ebselen: A Multifaceted Organoselenium Compound With Therapeutic Potential in Liver Diseases. (PubMed, Oxid Med Cell Longev) - "The hepatoprotective effects of Ebselen also extend to include reducing hepatic lipid accumulation and preventing steatosis induction in rodent models of liver fibrosis. This review summarizes the current available evidence on the hepatoprotective effects of Ebselen."

Journal • Review • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Reperfusion Injury

Selective probe for mapping peroxynitrite-accessible proteomes | Poster Board #1163 (ACS-Fall 2026) - "We describe Alkyne-NBESe, an -responsive probe that combines ebselen and Nile Blue scaffolds; this probe undergoes a reaction analogous to the Bamford–Stevens pathway, enabling the highly selective covalent labeling of proteins accessible to peroxynitrite...Importantly, PD-L1 was found to be accessible to peroxynitrite; site-specific nitration of PD-L1 at Tyr123 decreased its affinity for PD-1 by eight fold and abrogated immunosuppression. Collectively, these findings provide a chemical tool for mapping peroxynitrite-accessible proteomes and demonstrate that site-specific nitration serves as a modifiable mechanism for regulating PD-1/PD-L1 signaling."

IFNG

Ebselen inhibits PRRSV replication by activating the TRIM16/SQSTM1-KEAP1-NRF2-mediated oxidative stress response pathway. (PubMed, Vet Microbiol) - "In vivo challenge experiments further showed that Ebselen treatment significantly decreased pulmonary viral loads and alleviated lung histopathological damage. These findings support potential of Ebselen as a host-targeted antiviral strategy, highlighting its dual role in managing oxidative stress and inflammation, offering a promising approach to combat PRRSV."

Journal • Inflammation • Respiratory Diseases • KEAP1 • SQSTM1 • TRIM16

Mapping the covalent cysteine interactome of Ebselen reveals high-sensitivity target engagement and redox proteome remodeling. (PubMed, Bioorg Chem) - "Global TMT proteomics revealed extensive remodeling of redox-related and cell-survival-associated pathways, including compensatory upregulation of selenoproteins such as TXNRD1 and GPX family members. Together, these results define a chemical proteomic atlas of Ebselen-cysteine interactions and provide a framework for understanding and optimizing covalent organoselenium therapeutics."

Journal • Oncology • Targeted Protein Degradation

Innovations in conservative and surgical therapy for Ménière's disease-narrative review. (PubMed, Front Neurol) - "Clinical trial reports evaluating the efficacy of new oral treatment-ebselen were included. Preliminary report describing treating patients with MD and migaine with rimegepant was analyzed. Novel strategies to improve betahistine bioavailability were also reviewed...At the same time, these innovative therapeutic approaches provide valuable insights into the underlying pathophysiological mechanisms of the disease and may stimulate further research into its etiology. A better understanding of disease etiology is essential for developing causal treatments."

Journal • Review • Otorhinolaryngology • Vertigo

Promotion of Lead-induced Cytotoxicity in Differentiating Neural Cells and Protective Effects of Selenium. (PubMed, Biol Trace Elem Res) - "Moreover, the glutathione peroxidase (GPx) mimetic ebselen also alleviated Pb toxicity under these conditions. These findings indicate that selenium protects differentiating neural cells against Pb-induced injury through mechanisms involving peroxide-reducing activity as well as additional selenium-dependent pathways. Collectively, our findings provide new insights into the molecular basis of Pb-induced neurotoxicity and support a protective role for selenium-dependent stress resistance against Pb-induced cellular injury."

Journal • PRDX6 • SELENOP

Role of ROS, Soluble Guanylate Cyclase and cGMP in Mouse Lung Development During Hyperoxia. (PubMed, Am J Physiol Heart Circ Physiol) - "Those cells demonstrated impaired sGC-cGMP responsiveness to an NO donor, a response prevented by the cytosolic glutathione mimetic ebselen as well as by the sGC activator, cinaciguat, but not by mitochondrial matrix-targeted ebselen or by expression of an H2O2 scavenger in the mitochondrial intermembrane space (IMS-Prdx5). Neonatal mice exposed to 75% O2 for 2 weeks exhibited alveolar simplification and pulmonary artery (PA) wall thickening that were not rescued by cinaciguat or the sGC stimulator, riociguat...Collectively these studies demonstrate that separate mechanisms underlie the effects of hyperoxia on cGMP signaling and alveolarization in the newborn lung, with cytosolic oxidant stress responsible for impairing cGMP signaling and mitochondrial matrix ROS mediating the hyperoxia-induced impairment in lung alveolar development. Hence, the impairments in cGMP signaling and lung alveolar development during hyperoxia involve oxidant stress in distinct subcellular..."

Journal • Preclinical • Bronchopulmonary Dysplasia • Psychiatry • Pulmonary Disease • Respiratory Diseases • AVEN

Machine learning-guided discovery of covalent sortase A inhibitors targeting MRSA virulence. (PubMed, Eur J Med Chem) - "These inhibitors effectively disrupted MRSA biofilm formation at sub-inhibitory concentrations and significantly improved host survival in a Galleria mellonella infection model. Collectively, this study establishes a data-driven framework integrating machine learning and covalent chemistry for anti-virulence drug discovery and provides promising lead compounds targeting SrtA to combat MRSA infections."

Journal • Cognitive Disorders • Infectious Disease

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

Enrollment closed • Otorhinolaryngology

Revisiting the Radical Quenching Activity of Ebselen Analogues in Homogeneous Phase and In Silico Anti-ferroptotic Activity with Histone Deacetylase. (PubMed, Chembiochem) - "The high activity with high rate constants is attributed to the formation of a Se-centered conjugated dipolar transition state, where electron-donating substituents were found to enhance the radical quenching efficiency. Additionally, in silico studies revealed that all compounds exhibited favorable binding affinities toward the histone deacetylase 8 protein."

Journal • HDAC8

SPI-1005 Treatment in Severe COVID-19 Patients (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Sound Pharmaceuticals, Incorporated | Enrolling by invitation ➔ Completed | N=60 ➔ 25

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Tubulin as a Well-Established Yet Underexploited Target: New Opportunities for Drugs Repurposing? (PubMed, J Drug Target) - "Using nanoDSF, FDA-approved compounds were recently screened for effects on tubulin polymerization, identifying multiple previously unrecognized microtubule-targeting agents (MTA) including Auranofin, Ebselen, Riboflavin, Aprepitant, Benzarone and Nifedipine derivatives, etc. Many hits match reported microtubule perturbation or cancer-relevant phenotypes, and several have been considered for oncology repositioning. These observations suggest microtubule targeting may contribute to anticancer effects more often than appreciated and that tubulin remains an underexploited repurposing target. The aim of this review is to place these newly identified MTAs in the context of current knowledge and to discuss their potential for drug repurposing in oncology."

Journal • Review • Oncology

Ebselen-Loaded Silver-Containing Mesoporous Bioactive Glass for the Control of Enterococcus faecalis and Streptococcus mutans in Endodontic Infections. (PubMed, J Dent) - "The novel Ebselen/MBG-Ag bioceramic presents a dual-functional approach for endodontics. By simultaneously eliminating resilient bacterial biofilms and accelerating dentin remineralization via hydroxyapatite precipitation, it effectively targets the main drivers of root canal failure, offering a promising strategy to enhance long-term treatment success."

Journal • Infectious Disease

Study to Evaluate SPI-1005 in Adults With Meniere's Disease (clinicaltrials.gov) - P1/2 | N=40 | Completed | Sponsor: Sound Pharmaceuticals, Incorporated | Phase classification: P1b ➔ P1/2

Phase classification • Otorhinolaryngology

The Selenium Paradox: From Evolutionary Redox Chemistry to Medicinal Chemistry. (PubMed, Int J Mol Sci) - "However, despite extensive in vitro evidence and numerous publications, no organoselenium antioxidant has been commercialized, and even Ebselen, the most extensively studied selenium-based drug candidate, has repeatedly failed in multiple clinical trials...In a similar vein, undertaking a thorough examination of the mechanisms may facilitate a more profound comprehension of the fate of organoselenium compounds in their intricate interaction with biological targets. This, in turn, may enable the conception of novel molecules that function as effective and selective pro-oxidants against specific targets."

Journal • Review

Deazapurine-Based Cyclic Selenenyl Sulfide as a Glutathione Peroxidase Mimetic. (PubMed, Chemistry) - "Using these complementary approaches, we demonstrate that the selenenyl sulfide 6a catalyzes thiol oxidation with substantially higher efficiency than ebselen, a widely studied GPx mimic, under applied assay conditions. In addition, the compound exhibits exceptional chemical stability, with no NMR-detectable signs of degradation after two years of storage. These findings underscore the potential of cyclic selenenyl sulfides as GPx mimetics, providing a strong rationale for evaluating their catalytic properties in more complex chemical and biological contexts."

Journal

Bifunctional inhibitors of β-lactamases and ferroptosis: Design, synthesis and anti-gram-negative bacterial infection evaluation. (PubMed, Eur J Med Chem) - "In the murine intra-abdominal infection model, combined administration of E3f and meropenem markedly reduced bacterial loads in the liver and spleen compared with meropenem monotherapy. Collectively, these results confirm that E3f is a highly efficacious lead compound. Ebselen derivatives, which dually inhibit β-lactamases and produce ferroptosis-mediated anti-inflammatory activity, hold great promise as therapeutic agents against infections caused by MDR-GNB."

Journal • Acute Lung Injury • Infectious Disease • Inflammation • Respiratory Diseases • FTH1 • GPX4 • IL1B • IL6 • TNFA

Identification of inhibitors of an N- Monooxygenase from Aspergillus fumigatus. (PubMed, Biochimie) - "Ebselen derivative, ebsulfur, was also found to inhibit SidA with an IC50 value of 40 ± 13 μM. These compounds represent a new type of inhibitors of siderophore biosynthesis."

Journal • Infectious Disease