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Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach
The molecular revolution could lead drug discovery from chance observation to the rational design of new classes of drugs that could simultaneously be more effective and less toxic. Unfortunately, we are witnessing some failure in this sense, and the causes of the crisis involve a wide range of epis...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611316/ https://www.ncbi.nlm.nih.gov/pubmed/36297518 http://dx.doi.org/10.3390/pharmaceutics14102084 |
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author | Giuliani, Alessandro Fais, Stefano |
author_facet | Giuliani, Alessandro Fais, Stefano |
author_sort | Giuliani, Alessandro |
collection | PubMed |
description | The molecular revolution could lead drug discovery from chance observation to the rational design of new classes of drugs that could simultaneously be more effective and less toxic. Unfortunately, we are witnessing some failure in this sense, and the causes of the crisis involve a wide range of epistemological and scientific aspects. In pharmacology, one key point is the crisis of the paradigm the “magic bullet”, which is to design therapies based on specific molecular targets. Drug repurposing is one of the proposed ways out of the crisis and is based on the off-target effects of known drugs. Here, we propose the microenvironment as the ideal place to direct the off-targeting of known drugs. While it has been extensively investigated in tumors, the generation of a harsh microenvironment is also a phenotype of the vast majority of chronic diseases. The hostile microenvironment, on the one hand, reduces the efficacy of both chemical and biological drugs; on the other hand, it dictates a sort of “Darwinian” selection of those cells armed to survive in such hostile conditions. This opens the way to the consideration of the microenvironment as a convenient target for pharmacological action, with a clear example in proton pump inhibitors. |
format | Online Article Text |
id | pubmed-9611316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96113162022-10-28 Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach Giuliani, Alessandro Fais, Stefano Pharmaceutics Perspective The molecular revolution could lead drug discovery from chance observation to the rational design of new classes of drugs that could simultaneously be more effective and less toxic. Unfortunately, we are witnessing some failure in this sense, and the causes of the crisis involve a wide range of epistemological and scientific aspects. In pharmacology, one key point is the crisis of the paradigm the “magic bullet”, which is to design therapies based on specific molecular targets. Drug repurposing is one of the proposed ways out of the crisis and is based on the off-target effects of known drugs. Here, we propose the microenvironment as the ideal place to direct the off-targeting of known drugs. While it has been extensively investigated in tumors, the generation of a harsh microenvironment is also a phenotype of the vast majority of chronic diseases. The hostile microenvironment, on the one hand, reduces the efficacy of both chemical and biological drugs; on the other hand, it dictates a sort of “Darwinian” selection of those cells armed to survive in such hostile conditions. This opens the way to the consideration of the microenvironment as a convenient target for pharmacological action, with a clear example in proton pump inhibitors. MDPI 2022-09-29 /pmc/articles/PMC9611316/ /pubmed/36297518 http://dx.doi.org/10.3390/pharmaceutics14102084 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Perspective Giuliani, Alessandro Fais, Stefano Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title | Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title_full | Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title_fullStr | Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title_full_unstemmed | Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title_short | Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach |
title_sort | proposal to consider chemical/physical microenvironment as a new therapeutic off-target approach |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611316/ https://www.ncbi.nlm.nih.gov/pubmed/36297518 http://dx.doi.org/10.3390/pharmaceutics14102084 |
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