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Investigational New Drug Enabling Nonclinical Safety Pharmacology Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

Authors :
Shearer, Jeffry
Wolfe, Gary
Sampath, Aruna
Warfield, Kelly L
Kaufman, Brian
Ramstedt, Urban
Treston, Anthony
Source :
International Journal of Toxicology (Sage). May2022, Vol. 41 Issue 3, p201-211. 11p.
Publication Year :
2022

Abstract

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a broad-spectrum antiviral drug candidate with demonstrated activity in vitro and in vivo against multiple, diverse viruses. Nonclinical safety pharmacology studies were conducted to support the filing of an Investigational New Drug (IND) application. Preliminary in vitro pharmacology testing evaluating potential for binding to "off-target" receptors and enzymes indicated no significant liability for advanced development of UV-4. The safety pharmacology of UV-4 was evaluated in the in vitro human ether-à-go-go-related gene (hERG) assay, in a central nervous system (CNS) study in the mouse (modified Irwin test), in a respiratory safety study in conscious mice using whole body plethysmography, and in a cardiovascular safety study in conscious, radiotelemetry-instrumented beagle dogs. There were no observed adverse treatment-related effects following administration of UV-4 as the hydrochloride salt in the hERG potassium channel assay, on respiratory function, in the CNS study, or in the cardiovascular assessment. Treatment-related cardiovascular effect of decreased arterial pulse pressure after 50 or 200 mg of UV-4/kg was the only change outside the normal range, and all hemodynamic parameters returned to control levels by the end of the telemetry recording period. These nonclinical safety pharmacology assessments support the evaluation of this host-targeted broad-spectrum antiviral drug candidate in clinical studies. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10915818
Volume :
41
Issue :
3
Database :
Academic Search Index
Journal :
International Journal of Toxicology (Sage)
Publication Type :
Academic Journal
Accession number :
157176267
Full Text :
https://doi.org/10.1177/10915818211072842