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: firstname.lastname@example.org
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.
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