DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response.

The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation.

Efficacy of NVC-422 in the treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model.

Objectives: Dermatophytes, belonging to genera including Trichophyton, Epidermophyton, and Microsporum, are the causative agents of superficial fungal infections, prevalences of which are estimated to be as high as 25% in the worldwide population. This study evaluated the activity of topical formulations of NVC-422 (sodium 2-[dichloroamino]-2-methylpropane-1-sulfonate), the lead compound in a new class of antimicrobials that consist of broad-spectrum, fast-acting, nonantibiotic antimicrobial molecules based on the endogenously produced N-chlorotaurines.

Methods: The antifungal efficacy of NVC-422 was investigated using a guinea pig model of infection with Trichophyton mentagrophytes.

Virucidal mechanism of action of NVC-422, a novel antimicrobial drug for the treatment of adenoviral conjunctivitis.

Human adenoviral conjunctivitis is a highly contagious eye infection affecting millions of people world-wide. If untreated, it can further develop into keratitis, corneal ulceration, scarring and possible blindness. Despite the significant patient morbidity and socio-economic costs, it is an unmet medical need with no FDA approved treatment.

NVC-422 topical gel for the treatment of impetigo.

Impetigo is a highly contagious bacterial skin infection affecting children worldwide that is caused by the Gram-positive bacteria Staphylococcus aureus, Streptococcus pyogenes, or both. Staphylococcus species can quickly develop drug resistance rendering mupirocin, fusidic acid, and erythromycin ineffective. Preclinical and clinical studies demonstrated that NVC-422 (N, N-dichloro-2, 2-dimethyltaurine) rapidly kills pathogens without the development of drug resistance.

Identification of pretreatment agents to enhance adenovirus infection of bladder epithelium.

Adenovirus has been used widely as a gene transfer vector in the laboratory and clinic for the purpose of gene therapy. Conditionally replication-competent oncolytic adenoviruses are capable of multiplying up to a thousand old in target cells, a property that might prove to be of tremendous potential in the area of cancer therapy. Intravesicular therapy of refractory superficial bladder cancer employing an oncolytic adenovirus would allow for local administration and efficient delivery of virus to bladder tumor.