Why medicines work

The interactions of candidate medicines with physiology that have yielded therapeutics are a small subset of the total interactions investigated. To be useful the interactions must initiate molecular actions that fix a disease phenotype. While much is known about the targets for successful interacti...

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Veröffentlicht in:Pharmacology & therapeutics (Oxford) 2022-10, Vol.238, p.108175-108175, Article 108175
1. Verfasser: Swinney, David C.
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description The interactions of candidate medicines with physiology that have yielded therapeutics are a small subset of the total interactions investigated. To be useful the interactions must initiate molecular actions that fix a disease phenotype. While much is known about the targets for successful interactions and the disease phenotypes, much less is understood of the molecular actions that connect the initial interactions to specific phenotypic changes. Towards a better understanding of these actions, the first in class drugs (233) approved between 1999 and 2020 by the United States FDA were analyzed. The analysis identifies the actions that have been successful and characteristics of those actions. The medicines clustered into a relatively few specific actions: those that act on systems through sensors/receptors and controllers (51%), those that act to disrupt essential functions (12%), and those that act to provide a molecular fix by repair, removal, or silencing (33%). Antimicrobials were clustered with those that disrupt essential functions and antivirals were clustered in the molecular category. The sensor and controller actions work through system specific regulatory nodes whereby a single modality triggers a change to a complex system. Actions that disrupt functions cause toxicity and death to cells and organisms, where in many cases, mechanisms of repair and compensation play a role in both death and specificity. The molecular actions directly address known disease causes and arise from the intersection between enabling technologies that identify disease cause, and development of new modalities and their corresponding actions that provide therapeutic solutions. Many of the medicines utilize physiologic processes involving committed transitions at the core of the actions to enhance specificity. These actions, which process the input to specific output, are important for understanding why medicines work.
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subjects Drug action
Drug discovery
Mechanism
Medicines
Pharmacology
Physiologic context
title Why medicines work
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