​Nitric Oxide Prodrugs

Nitric oxide is an endogenously produced free radical released by cells as part of the innate immune response to pathogens. Nitric oxide is a unique alternative to antibiotics because it has unparalleled broad-spectrum antimicrobial activity compared to existing drugs.  Furthermore, nitric oxide kills bacteria via multiple mechanisms, including nitrosative and oxidative stresses that damage DNA, lipid membranes, proteins, and iron-sulfur clusters. 

Vast is developing nitric oxide prodrugs that can be inhaled on demand using dry powder inhalers, meter dose inhalers, or aerosolized solution formulations to target a broad range of severe respiratory infections.  Once deposited in the lungs, the prodrugs begin to degrade with total nitric oxide release durations ranging from 1 to 24 hours depending on the specific chemistry.  

The company has broad, worldwide patent rights including an exclusive license to four issued patents and pending patent applications as well as its own pending patent applications.  The issued patents cover multiple nitric oxide-releasing compounds and their pharmaceutical formulations.  In addition, the pending patent applications cover additional nitric oxide related materials and uses.

Publications

Exogenous Nitric Oxide Improves Antibiotic Susceptibility in Resistant Bacteria
​Kaitlyn R. Rouillard, Olivia P. Novak, Alex M. Pistiolis, Lei Yang, Mona J. R. Ahonen, Rebecca A. McDonald, and Mark H. Schoenfisch, ACS Infect. Dis. 2021, 7, 1, 23–33.

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Pseudomonas aeruginosa Biofilm Eradication via Nitric Oxide-Releasing Cyclodextrins
​Kaitlyn R. Rouillard, Matthew R. Markovetz, Lawrence G. Bacudio, David B. Hill, and Mark H. Schoenfisch, ACS Infect. Dis. 2020, 6, 7, 1940–1950.

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Nitric oxide-releasing alginates as mucolytic agents
​Mona Jasmine R. Ahonen, David B. Hill, Mark H. Schoenfisch, ACS Biomater Sci Eng. 2019 July 8; 5(7): 3409–3418. doi:10.1021/acsbiomaterials.9b00482.

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Antibiofilm and mucolytic action of nitric oxide delivered via gas or macromolecular donor using in vitro and ex vivo models
​Kaitlyn R. Rouillarda, David B. Hillb, Mark H. Schoenfisch, ​J Cyst Fibros. 2020 November ; 19(6): 1004–1010. doi:10.1016/j.jcf.2020.03.004.

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Antibiofilm efficacy of nitric oxide-releasing alginates against cystic fibrosis bacterial pathogens
​Mona Jasmine R. Ahonen, Jamie M. Dorrier, Mark H. Schoenfisch, ACS Infect Dis. 2019 August 09; 5(8): 1327–1335. doi:10.1021/acsinfecdis.9b00016.

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Nitric oxide diffusion through cystic fibrosis-relevant media and lung tissue
​Jackson R. Hall, Sara E. Maloney, Haibao Jin, James B. Taylor and Mark H. Schoenfisch, RSC Adv., 2019, 9, 40176.

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Role of Nitric Oxide-Releasing Chitosan Oligosaccharides on Mucus Viscoelasticity
​Katelyn P. Reighard, Camille Ehre, Zachary L. Rushton, Mona Jasmine R. Ahonen, David B. Hill, and Mark H. Schoenfisch, ACS Biomater Sci Eng. 2017 ; 3(6): 1017–1026. doi:10.1021/acsbiomaterials.7b00039.

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