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Printable Handouts
Navigable Slide Index
- Introduction
- Drug discovery is an iterative process
- Challenges to drug discovery productivity
- Outline - learning from past success
- The therapeutic index drives drug discovery
- Drug discovery has a strategy and starting point
- Chronology of approaches to identify new drugs
- Types of drug discovery
- Definitions of first in class and follower
- How were new medicines discovered?
- Drugs discovered with phenotypic screening
- Drugs discovered with target-based screening
- Natural substances provided starting points
- Biologics classification
- No lag in distribution by discovery strategy
- NMEs first in class discovery by therapeutic area
- We have revealed a paradox
- MMOA is at the core of the paradox
- What is MMOA?
- Communication as an analogy of MMOA
- Kinetics differentiate medicines
- Conformation differentiate medicines
- Binding to transient conformational state
- Schematic of drug action
- Why is MMOA important?
- Competition and drug activity
- Biochemical efficiency
- KI/EC50 is influenced by numerous factors
- Slow binding kinetics can limit competition
- MMOAs of approved medicines
- Drug classes evolve over time
- Optimal MMOA and mechanism-based toxicity
- How to identify an optimal MMOA?
- Diverse MMOAs
- Target alone is not sufficient
- Approved medicines have many diverse MMOAs
- Learning
- Practical considerations for drug discovery
- Hopes for rational gene to patient drug discovery
- Balance between empirical & molecular approach
- Brief summary
- Acknowledgements
Topics Covered
- Drug discovery strategies
- How drugs were discovered
- The paradox between empirical and hypothesis driven drug discovery
- How drugs work/molecular mechanism of action is at the core of the paradox
- Practical application of new knowledge
Talk Citation
Swinney, D. (2013, September 23). Where did drugs come from? [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 14, 2024, from https://doi.org/10.69645/JIFD6029.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. David Swinney has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Pharmaceutical Sciences
Transcript
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0:00
Hello, this is David Swinney.
I'm going to be talking to you about where drugs come from.
I'm currently at the Institute for Rare and Neglected Diseases Drug Discovery,
a non-profit recently formed to discover drugs for rare and neglected diseases.
Before that, I was at Roche in Palo Alto for 20 years, where we did much of the work that we will talk about in this presentation.
0:29
Drug discovery is an iterative process starting with an unmet medical need and an idea to address that need.
From that idea, you'll get a starting point, which could be a small molecule or an assay,
which will then eventually lead to a drug candidate through an optimization process.
From that drug candidate, it will then go into clinical testing initially with safety, proof-of-concept and finally, larger phase three studies leading to registration.
What I've tried to show in this slide is how it's really an iterative process with many different cycles that feed back on each other, which can gain knowledge.
You can actually measure this through different kinds of markers, biomarkers, the success or lack of success at each stage in the process.
1:22
A challenge to productivity is the time and investment required to identify medicines that are both efficacious and safe.
Candidates for clinical trials will succeed or fail based on their own merits.
Most candidates will fail.
How can candidates be identified with a better chance for success?
The intention with this work was to learn from past success.
We've evaluated the role of how a medicine will work at the molecular level,
as well as work to understand how medicines and the respective molecular mechanisms were discovered.