Prodrugs: Design and Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (25 March 2025) | Viewed by 2482

Special Issue Editors


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Guest Editor
Organic Chemistry Chair II, Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Nikolaus-Fiebiger-Str. 10, 91058 Erlangen, Germany
Interests: drug development; cancer research; cell biology; organelle targeting; metalorganics

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Guest Editor
1. School of Pharmaceutical Science, State University of São Paulo (UNESP), São Paulo, Brazil
2. School of Medicine, Union of the Colleges of the Great Lakes (UNILAGO), SJRP, São Paulo, Brazil
Interests: new drugs; drug design; drug discovery; infectious disease; medicinal chemistry

Special Issue Information

Dear Colleagues,

Chemically modified drug molecules with a neglectable pharmacological activity that are transformed into the active parent drug in vivo by enzymatic reactions or under special cellular conditions are called prodrugs. The concept of the prodrug is designed to tackle several drug formulation and pharmacokinetic problems including poor solubility, low absorption, too-high or too-low lipophilicity, and poor target discrimination. As a result, every year the United States Food and Drug Administration (FDA) approves several prodrugs which account for a significant fraction (>10%) of all FDA-approved small molecules. Some recent examples are Eybelis (topical ocular hypotensive treatment, approved in 2022) and Azstarys (attention deficit hyperactivity disorder treatment, approved in 2021).

This Special Issue is dedicated to the design and development of prodrugs, the in vivo and in vitro studies as well as to the development of advanced drug-delivery systems with prodrug mechanism of action, such as prodrug-based nanoparticles. Authors are welcome to submit research papers or review articles on the topics connected with prodrug carriers, the development of not-selective prodrugs to improve drug pharmacokinetic properties, or the development of selective prodrugs activated by light, disease-specific enzymes, hypoxic/oxidative microenvironment of cancer and/or pH, etc.

Dr. Viktor Reshetnikov
Prof. Dr. Chung Man Chin
Guest Editors

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Keywords

  • prodrug
  • molecular modification
  • disease-specific activation
  • targeting
  • solubility and lipophilicity adjustment

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Published Papers (1 paper)

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Review

37 pages, 9366 KiB  
Review
Current Trends in Clinical Trials of Prodrugs
by Diogo Boreski, Valentine Fabienne Schmid, Priscila Longhin Bosquesi, Jean Leandro dos Santos, Cauê Benito Scarim, Viktor Reshetnikov and Chung Man Chin
Pharmaceuticals 2025, 18(2), 210; https://doi.org/10.3390/ph18020210 - 4 Feb 2025
Viewed by 1659
Abstract
The development of new drugs is a lengthy and complex process regarding its conception and ideation, passing through in silico studies, synthesis, in vivo studies, clinical trials, approval, and commercialization, with an exceptionally low success rate. The lack of efficacy, safety, and suboptimal [...] Read more.
The development of new drugs is a lengthy and complex process regarding its conception and ideation, passing through in silico studies, synthesis, in vivo studies, clinical trials, approval, and commercialization, with an exceptionally low success rate. The lack of efficacy, safety, and suboptimal pharmacokinetic parameters are commonly identified as significant challenges in the discovery of new drugs. To help address these challenges, various approaches have been explored in medicinal chemistry, including the use of prodrug strategies. As a well-established approach, prodrug design remains the best option for improving physicochemical properties, reducing toxicity, and increasing selectivity, all while minimizing costs and saving on biological studies. This review article aims to analyze the current advances using the prodrug approach that has allowed the advance of drug candidates to clinical trials in the last 10 years. The approaches presented here aim to inspire further molecular optimization processes and highlight the potential of this strategy to facilitate the advancement of new compounds to clinical study phases. Full article
(This article belongs to the Special Issue Prodrugs: Design and Development)
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