uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Discovery and preclinical development of new antibiotics
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
2014 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, 162-169 p.Article, review/survey (Refereed) Published
Abstract [en]

Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

Place, publisher, year, edition, pages
2014. Vol. 119, no 2, 162-169 p.
Keyword [en]
Candidate drug, efficacy, hit molecule, lead molecule, liability testing, medicinal chemistry
National Category
Medicinal Chemistry
URN: urn:nbn:se:uu:diva-228436DOI: 10.3109/03009734.2014.896437ISI: 000336526100015OAI: oai:DiVA.org:uu-228436DiVA: diva2:734073
Available from: 2014-07-14 Created: 2014-07-14 Last updated: 2014-07-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Hughes, DiarmaidKarlén, Anders
By organisation
MicrobiologyOrganic Pharmaceutical Chemistry
In the same journal
Upsala Journal of Medical Sciences
Medicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 673 hits
ReferencesLink to record
Permanent link

Direct link