Novel Agents and Drug Targets to Meet the Challenges of Resistant Fungi

McCarthy, Matthew W; Kontoyiannis, Dimitrios P.; Cornely, Oliver A.; Perfect, John R.; Walsh, Thomas J.

doi:10.1093/infdis/jix130

Cited by 151 publications

(116 citation statements)

References 118 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…All of the most important groups of antibiotics (tetracyclines, cephalosporins, aminoglycosides and macrolides) were discovered in the 1960s and these compounds are in danger of losing their efficacy because of the increase in microbial resistance [20], due especially to the emergence of multidrug-resistant bacteria [21,22,23]. For this reason, the discovery of new antibiotics is one of the main objectives of medicine nowadays [24].…”

Section: Methodologies Of Screeningmentioning

confidence: 99%

Current Screening Methodologies in Drug Discovery for Selected Human Diseases

et al. 2018

View full text Add to dashboard Cite

The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered. For drug discovery, two different complementary approaches can be applied: classical pharmacology, also known as phenotypic drug discovery, which is the historical basis of drug discovery, and reverse pharmacology, also designated target-based drug discovery. Screening methods based on phenotypic drug discovery have been used to discover new natural products mainly from terrestrial origin. Examples of the discovery of marine natural products are provided. A section on future trends provides a comprehensive overview on recent advances that will foster the pharmaceutical industry.

show abstract

Section: Methodologies Of Screeningmentioning

confidence: 99%

Current Screening Methodologies in Drug Discovery for Selected Human Diseases

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Gegenwärtig werden fünf Klassen antimykotischer Mittel zur Behandlung von Pilzinfektionen beim Menschen verwendet: [358,359] [360][361][362] wird sich dieser Te il des Aufsatzes auf die grçßte und am meisten untersuchte dieser Klassen, die Azole,k onzentrieren und ihre Wirkungsweise,ihre Widerstandsmechanismen und die gegenwärtigen Entwicklungen hervorheben. …”

Section: Einführungunclassified

Eine strukturelle Evaluierung medizinalchemischer Strategien gegen Wirkstoffresistenzen

Agnello¹,

Brand²,

Chellat³

et al. 2019

Angewandte Chemie

View full text Add to dashboard Cite

Das natürliche Phänomen der Wirkstoffresistenz stellt eine universelle Beeinträchtigung des Nutzens von pharmazeutischen Wirkstoffen in vielen klinischen Indikationen dar. Antibakterielle und antifungale Wirkstoffe sind dabei ebenso betroffen wie Wirkstoffe zur Behandlung von Krebs, Virusinfektionen oder durch Parasiten hervorgerufene Erkrankungen. Trotz der unterschiedlichen biologischen Zielstrukturen und Organismen, die bei der Entwicklung von Wirkstoffresistenzen involviert sind, konnten grundlegende molekulare Prozesse identifiziert werden, die zum Verständnis des Auftretens von Resistenzen beitragen und die Bekämpfung dieser nachteiligen Mechanismen erlauben. Strukturelle Informationen über die Prinzipien von Wirkstoffresistenzen sind heute vielfältig vorhanden, sodass neue Wirkstoffe entwickelt werden können, die weniger anfällig gegenüber einer Resistenzbildung sein werden. Dieser wissensbasierte Ansatz ist eine Grundlage für den Kampf gegen das unvermeidbare Auftreten von Wirkstoffresistenzen.

show abstract

“…Nevertheless, it is crucial that such treatments for emerging IFDs and for IFDs in special patient populations are evaluated, even when there are multiple obstacles to the performance of robust studies. New drug classes with activity against azole‐resistant fungal species are currently in clinical development (eg tetrazoles, pyrimidine synthesis inhibitors, glycosylphosphatidylinositol inhibitors) and they are facing similar study‐design challenges. It is hoped that future improvements and integration of biomarkers and radiography might be used to enhance assessment of the impact of antifungal agents in these patients.…”

Section: Lessons From the Vital Trialmentioning

confidence: 99%

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial

Perfect

Cornely

Heep

et al. 2018

Mycoses

View full text Add to dashboard Cite

Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator.

show abstract

Novel Agents and Drug Targets to Meet the Challenges of Resistant Fungi

Cited by 151 publications

References 118 publications

Current Screening Methodologies in Drug Discovery for Selected Human Diseases

Current Screening Methodologies in Drug Discovery for Selected Human Diseases

Eine strukturelle Evaluierung medizinalchemischer Strategien gegen Wirkstoffresistenzen

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial

Contact Info

Product

Resources

About