Volume 5, 2022
Proteomics, Proteolysis and Amyloid beta
|Number of page(s)||8|
|Section||Life Sciences - Medicine|
|Published online||04 July 2022|
Rampant proteolysis at the intersection of therapy-induced hypoalbuminemia and acute pancreatitis
From the Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
2 New Liberty Proteomics Corporation, New Liberty, KY 40355, USA
* Corresponding author: email@example.com
Accepted: 18 May 2022
Protease inhibition is the intended mechanism of action for drugs across a broad range of diseases: cancer, cardiovascular and stroke, diabetes mellitus, macular degeneration and Alzheimer’s. Treatment for fungal and multiple viral infections, including Sars-Cov-2, also relies upon inhibition of pathogen-specific proteases. This work examines the non-therapeutic proteolytic activity of one such drug, nelfinavir (tradename VIRACEPT™), approved as an inhibitor of HIV protease, the largest, “biotech launch” in history at the time of its introduction. Methods are described in the companion manuscript [Leonard et al. (2022), 4open 5, 11]. These methods are not only suitable for examination of on-target activity but also of off-target activity. Herein, it is demonstrated that nelfinavir is active both as an inhibitor and as a promoter of proteolysis of key blood proteins. Observations are readily connected to known drug induction of acute pancreatitis and attendant hypoalbuminemia. The benefits of expanding molecular-level, early-stage, off-target/off-substrate activity drug candidate evaluation become apparent. Finally, the reality of drug-induced disease places new demands on existing clinical procedures, namely that side effects be approached as symptoms of an induced disease.
Key words: Proteolysis / Hypoalbuminemia / Acute pancreatitis
© S.-E. Leonard et al., Published by EDP Sciences, 2022
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.