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Strengths and limitations of phenotypic drug discovery
Published on August 30, 2022 29 min
A selection of talks on Pharmaceutical Sciences
RNA therapeutics: clinical applications and methods of delivery
- Prof. John P. Cooke
- Houston Methodist Research Institute, USA
Overview of nonclinical safety assessment
- Dr. Claudette L. Fuller
- Merck Research Laboratories, USA
Drug-induced liver injury: risk factors and drug development in DILI
- Prof. James H. Lewis
- Georgetown University Medical Center, USA
Drugging conformational states of GPCRs
- Prof. Dr. Peter Kolb
- Philipps-Universität Marburg, Germany
In this talk, I'm going to discuss the strengths and limitations of phenotypic drug discovery. I'm Dr. Jonathan Cox, Senior Lecturer in Microbiology at Aston University.
In this talk, I'm going to cover a few key things. The first of which is, why we need new antibiotics, what I like to call 'The Urgent Need'. I'm then going to discuss different approaches to antibiotic discovery. Then I'm going to run through a couple of case studies. The first of which will cover phenotypic drug discovery. The second one will clearly demonstrate the limitations of phenotypic drug discovery.
Why do we need antibiotics? This figure from the O'Neill review on antimicrobial resistance, exemplifies the importance of finding new antibiotics. Currently, 700,000 people a year die from antibiotic-resistant infections. That number is estimated to rise to 10 million people by 2050 if we do nothing about it. Antibiotic resistance could overtake cancer as the leading cause of death within our lifetime. This is why it's imperative we discover new antibiotics.
What antibiotics do we really need? Well, antibiotics are powerful selective poisons. They kill bacteria, but they don't kill us. They're a magic bullet if you like. We need antibiotics that can work like this, but that are able to overcome existing mechanisms of antibiotic resistance. We don't want to create a selection pressure for more resistance ideally. We need highly regulated and restricted use of these new antibiotics and/or we want to easily modify these antibiotics to produce second and third line drugs should antibiotic resistance to that class emerge. Importantly, they need to be cheap to produce. They need a broad spectrum of activity. They need to be useful to treat the full range of bacterial pathogens, the A to Z, from Acinetobacter through to Yersinia. I couldn't think of a bacterial Z. The 2017 estimate puts the cost of developing