Polypharmacology in Clinical Applications: Renal Polypharmacology

Wang, Zhiguo; Yang, Baofeng

doi:10.1007/978-3-031-04998-9_9

Cited by 2 publications

(1 citation statement)

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“…Medicinal polypharmacology also stretches far into the very basis of drug design, discovery, and development itself (Anighoro et al, 2014; Proschak et al, 2019). Multitarget agents allow not only for addressing multiple druggable targets of the addressable “diseasome” (Wang & Yang, 2022); they also reach into a network of (yet) undruggable targets by either of two ways: (i) impact on a druggable target which subsequently reaches into a network of undruggable targets by a known or unknown pathway; or (ii) direct interaction with the to this point undruggable target itself (Korcsmaros et al, 2007). Multitarget agents are suitable ligands to de‐orphanize undruggable targets: …”

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confidence: 99%

Medicinal polypharmacology: Exploration and exploitation of the polypharmacolome in modern drug development

Stefan,

Rafehi

2023

Drug Development Research

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At the core of complex and multifactorial human diseases, such as cancer, metabolic syndrome, or neurodegeneration, are multiple players that cross‐talk in robust biological networks which are intrinsically resilient to alterations. These multifactorial diseases are characterized by sophisticated feedback mechanisms which manifest cellular imbalance and resistance to drug therapy. By adhering to the specificity paradigm (“one target‐one drug concept”), research focused for many years on drugs with very narrow mechanisms of action. This narrow focus promoted therapy ineffectiveness and resistance. However, modern drug discovery has evolved over the last years, increasingly emphasizing integral strategies for the development of clinically effective drugs. These integral strategies include the controlled engagement of multiple targets to overcome therapy resistance. Apart from the additive or even synergistic effects in therapy, multitarget drugs harbor molecular‐structural attributes to explore orphan targets of which intrinsic substrates/physiological role(s) and/or modulators are unknown for future therapy purposes. We designated this multidisciplinary and translational research field between medicinal chemistry, chemical biology, and molecular pharmacology as ‘medicinal polypharmacology’. Medicinal polypharmacology emerged as alternative approach to common single‐targeted pharmacology stretching from basic drug and target identification processes to clinical evaluation of multitarget drugs, and the exploration and exploitation of the ‘polypharmacolome’ is at the forefront of modern drug development research.

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