Prodrugs--from Serendipity to Rational Design (original) (raw)
Related papers
Review:, Prodrug Concept In Drug Design
المجلة الليبية العالمية, 2017
In the world of drug discovery and development, prodrugs have become a powerful method for improving biopharmaceutical, physicochemical or pharmacokinetic properties of pharmacologically active agents. The purpose of this review is to provide some types of prodrugs which are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. The target of prodrug design is to beat the undesirable drug properties, such as low target selectivity, low solubility in water or lipid membranes, chemical instability, irritation or pain after local administration, presystemic toxicity and metabolism. In this article, we focused on to describe the basic functional groups that are amenable to prodrug design and highlight the major applications of the prodrug strategy. Furthermore, the concepts of prodrug and the classifications of prodrugs will be offered in this article.
The expanding role of prodrugs in contemporary drug design and development
Nature reviews. Drug discovery, 2018
Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two. Prodrugs have evolved from being serendipitously discovered or used as a salvage effort to being intentionally designed. Such efforts can avoid drug development challenges that limit formulation options or result in unacceptable biopharmaceutical or pharmacokinetic performance, or poor targeting. In the past 10 years, the US Food and Drug Administration has approved at least 30 prodrugs, which accounts for more than 12% of all approved small-molecule new chemical entities. In this Review, we highlight prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs. We also discuss preclinical and clinical challenges and considerations in prodrug design and development.
Prodrugs: A challenge for the drug development
It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug. They are designed in order to improve the physicochemical, biopharmaceutical and/or pharmacokinetic properties of pharmacologically potent compounds. This article describes the basic functional groups that are amenable to prodrug design, and highlights the major applications of the prodrug strategy, including the ability to improve oral absorption and aqueous solubility, increase lipophilicity, enhance active transport, as well as achieve site-selective delivery. Special emphasis is given to the role of the prodrug concept in the design of new anticancer therapies, including antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT).
Prodrug Approach: An Alternative to Improve Pharmacokinetic Properties
International Journal of Bioorganic Chemistry
Prodrugs are the masked forms of active drugs that are designed to be activated once they have been administered into the body by an enzymatic or chemical means. It is a well known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their undesirable pharmacokinetic properties and decrease their toxicity. In most of the cases, prodrugs design involves the introduction of carrier/promoiety by a metabolic liable linkage so that after biotransformation by one or two chemical or enzymatic steps it will lead to the active parent drug. However, some prodrugs lack an obvious promoiety but instead result from a molecular modification of the prodrug itself, which generates a new active compound. This review introduces in depth the rationale behind the use of the promoiety, and also considers the possible problems that can arise from inadequate activation of prodrugs.
Highly Efficient Prodrugs: Design and Therapeutic Applications
2020
Prodrug is a very powerful way for the improvement of biopharmaceutical, physicochemical, or pharmacokinetic possessions of pharmacologically dynamic mediators. Prodrug is a pharmacologically not an active compound, which can be converted into an active drug by biotransformation which is metabolic and such process the efficiency of drugs gets improved with specific target delivery. The conversion of a prodrug to drug may happen before concentration, after concentration, or at a precise part of the physique. This approach has many advantages over drug administration which is in our convention. In this review, different types of carriers, which can be used for prodrug synthesis are summarized. Examples of both marketed and investigational prodrugs from several promoieties are discussed not only for their advantages and uses but also their prospects. The purpose of this review is to introduce in detail the foundation behind the use of the prodrug methodology from past to present, and a...
2015
A prodrug is a precursor chemical compound of a drug. Instead of administering a drug, a prodrug might be used instead to improve how a medicine is absorbed, distributed, metabolized, and excreted (ADME).A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor bio-logical activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug.Prodrugs are bio reversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. In both drug discovery and development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of ph...
Prodrugs-Curent and Future Drug Development Strategy
The focus of traditional prodrug approach was on altering various physiochemical parameters, whereas the current modern computational approach considers designing prodrugs through attaching appropriate linkers with drugs having poor bioavailability which upon exposure to physiological environments release the parent active drugs in a programmable (controlled) manner resulting in an improvement of their bioavailability. With the possibility of designing prodrugs with different linkers, the release rate of the parent active drugs can be controlled. The future of prodrug technology is exciting and yet challenging. Advances must be made in understanding the chemistry of many organic reactions that can be effectively utilized to enable the development of more types of prodrugs. The understanding of organic reaction mechanisms of certain processes, particularly intramolecular reactions, will be the next major milestone in this field. It is envisioned that the future of prodrug technology holds the ability to create safe and efficacious delivery of a wide range of active small molecules and biotherapeutics. This goal can be achieved using computational chemistry methods such as ab initio, semi-empirical and density functional theory (DFT), and molecular mechanics (MM) to calculate physicochemical and molecular properties of current marketed drugs suffer low bioavailability or/and unpleasant taste or odor. IJMPCR, Article no. IJMPCR.2014.009 59
LATENTIATED PRODRUG APPROACH OF DRUGS: AN OVERVIEW Review Article
International Journal of Applied Pharmaceutics, 2021
Prodrugs, with their capability of declining the adverse events and elevating the bioavailability of certain drugs, have captured enormous attention throughout the world since the 20 th century. The versatility of the prodrugs that are inert and after administration releasing the parent moiety for the desired effect has become a major criterion for the scientists to incorporate this to alleviate the undesired effects of a conventional drug. About 10% of the prevailing drugs are prodrugs and their usage is being amplified owing to its critical application in cancer therapy, toxicity alleviation, and specificity. The purpose of this review is to understand the prodrugs, strategies incorporated in designing the prodrugs, applications, their crucial benefits in targeted action at a specific site of the body, their advantageous effects in chemotherapy. Also, to be acknowledged with the ongoing clinical trials and researches on prodrugs and some notable marketed prodrugs in a depth manner.