Prodrug Strategies in Drug Design

Rautio, Jarkko

doi:10.1002/9783527633166.ch1

Cited by 8 publications

(10 citation statements)

References 88 publications

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“…• Various different prodrug methods GI, gastrointestinal. 752 implementation of the prodrug approach, almost 15% of the 100 best-selling small-molecular-weight drugs in 2009 were prodrugs (Table 2) (Rautio, 2010). One interesting example of these blockbuster prodrugs is lisdexamfetamine dimesylate (Vyvanse), the L-lysine prodrug of the psychostimulant dextroamphetamine, which was designed to have less abuse potential than other amphetamines due to the slower release of the active parent drug if inhaled or injected.…”

Section: History and The Present Of Prodrug Designmentioning

confidence: 99%

“…1) (Ettmayer et al, 2004;Rautio et al, 2008;Rautio, 2010;Stella, 2010). Prodrugs are considered to be inactive or at least significantly less active than the released drugs; therefore, salts of active agents and drugs, whose metabolites contribute to the overall pharmacological response, are not included in this definition.…”

Section: Introductionmentioning

confidence: 99%

“…A very good indication of the success of the prodrug approach can be obtained by examining the prevalence of prodrugs on the market. It might come as a surprise to many people that currently approximately 10% of all globally marketed medicines can be classified as prodrugs, and in 2008 alone, 33% of all approved small-molecular-weight drugs were prodrugs (Rautio, 2010;Stella, 2010). Despite these impressive numbers, we have only begun to appreciate the full potential of the prodrug approach in modern drug development, and many novel prodrug innovations await discovery.…”

Section: Introductionmentioning

confidence: 99%

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Prodrugs—from Serendipity to Rational Design

2011

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Section: History and The Present Of Prodrug Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prodrugs—from Serendipity to Rational Design

2011

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“…It is administered in an inactive form, and it must convert or hydrolyze to its active form through physiological metabolism 7 8 . As estimated, prodrugs accounted for about 17.8% (34 of the 191) of new chemical entities approved between 2000 and 2008, and prodrug prevalence was 15.4% among the top 100 bestselling small molecular weight drugs in 2008 9 10 .…”

mentioning

confidence: 99%

Programmed Hydrolysis in Designing Paclitaxel Prodrug for Nanocarrier Assembly

Wang

et al. 2015

Sci Rep

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Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency. For therapeutic efficacy, the prodrug must hydrolyze to its parent drug after administration. Based on the fact that the hydrolysis is impeded by steric hindrance and improved by sufficient polarity, in this study, we proposed the PTX-S-S-VE, the conjugation of paclitaxel (PTX) to vitamin E (VE) through a disulfide bridge. This conjugate possessed the following advantages: first, it can be encapsulated in the VE/VE2-PEG2000/water nanoemulsions because of favorable hydrophobic interactions; second, the nanoemulsions had a long blood circulation time; finally, the concentrated glutathione in the tumor microenvironment could cleave the disulfide bond to weaken the steric hindrance and increase the polarity, promoting the hydrolysis to PTX and increasing the anticancer activity. It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased. In addition, PTX-S-S-VE had greater anticancer activity against the KB-3-1 cell line tumor xenograft and the tumor size was smaller after the 4th injection. The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

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“…1). This molecule is similar to paracetamol 4 and methenamine 5 . Under acidic condition, methenamine degrades to formaldehyde and ammonia.…”

Section: Introductionmentioning

confidence: 65%

Highly Efficient Prodrugs: Design and Therapeutic Applications

Pal¹,

Banik

2020

Orient. J. Chem

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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 at the same time, to consider the possible consequences, which may evolve from insufficient initiation of prodrugs. Furthermore, the concept of prodrug and the classifications of prodrugs will be discussed in this article and it is expected that this review will be helpful for medicinal chemists for their research in the upcoming days.

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Prodrug Strategies in Drug Design

Cited by 8 publications

References 88 publications

Prodrugs—from Serendipity to Rational Design

Prodrugs—from Serendipity to Rational Design

Programmed Hydrolysis in Designing Paclitaxel Prodrug for Nanocarrier Assembly

Highly Efficient Prodrugs: Design and Therapeutic Applications

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