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. Manuscripts covering our technology and nitric oxide's broad spectrum antimicrobial activity published by Founder and Chief Scientific Officer, Dr. Mark Schoenfisch are listed below. |
Publications
Nitric oxide-releasing prodrug for the treatment of complex Mycobacterium abscessus infections
Rebecca A. McDonald, Sarah G. Nagy, Madyson Chambers, Chris A. Broberg, Mona J. R. Ahonen, Mark H. Schoenfisch, ASM Journals. doi:10.1128/aac.01327-23. 2024 Jan 11. |
Nitric Oxide-Induced Morphological Changes to Bacteria
Nguyen HK, Picciotti SL, Duke MM, Broberg CA, Schoenfisch MH, ACS Infect Dis. 2023 Nov 10;9(11):2316-2324. doi: 10.1021/acsinfecdis.3c00415. Epub 2023 Oct 13. PMID: 37831756. |
Biofilm Dispersal, Reduced Viscoelasticity, and Antibiotic Sensitization via Nitric Oxide-Releasing Biopolymers
Grayton QE, Nguyen HK, Broberg CA, Ocampo J, Nagy SG, Schoenfisch MH, ACS Infect Dis. 2023 Sep 8;9(9):1730-1741. doi: 10.1021/acsinfecdis.3c00198. Epub 2023 Aug 11. PMID: 37566512. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |