2019 Monash 3MT Winner - Beatrice Chiew, Pharmacy and Pharmaceutical Sciences

Summary

Beatrice Shu from the Faculty of Pharmacy and Pharmaceutical Sciences embarks on 'SAR Wars,' an innovative approach to drug discovery. She explores chemical space, the vast array of potential therapeutic compounds, and introduces two strategies to efficiently navigate it. Shu's project aims to enhance the odds of finding effective drugs by designing diverse chemical libraries and utilizing off-rate screening, a technique that identifies promising drug leads without the need for purification. Her work has already yielded three promising candidates for breast cancer treatment, showcasing the potential to save billions in drug discovery costs.

Takeaways

• 🎓 Beatrice Shu from the Faculty of Pharmacy and Pharmaceutical Sciences discusses her project on improving drug discovery through efficient chemical space exploration.
• 🌌 Chemical space refers to the vast number of possible therapeutic compounds, limited to commonly found elements and realistic connections, resulting in a large number of combinations.
• 💊 To be a drug, a chemical must fit well to a protein that is key to a disease, but only a tiny fraction of chemicals in chemical space meet this criterion.
• 💸 Drug discovery is an expensive process, with billions of dollars invested annually, but with no guarantee of yielding a successful drug.
• 🚀 Beatrice aims to improve the odds of finding useful drugs by making the process of exploring chemical space more efficient, likening it to the Kessel run in 'Star Wars'.
• 🗺️ Structure-activity relationships (SAR) are maps that relate the structure of a chemical to its effect on a protein, which are crucial for drug discovery but are costly to create.
• 🧪 The first strategy to combat SAR wars involves designing large libraries of structurally diverse chemicals that can be made in small volumes.
• 🔬 The second strategy is off-rate screening, a technique that allows testing of chemical libraries without purification by measuring how well chemicals fit to proteins based on their off-rate.
• 💡 Off-rate screening is significant because only chemicals that fit well to proteins will have a slow off-rate, allowing for the identification of promising drug leads without the need for purification.
• 🔑 Beatrice has applied these strategies to fight against breast cancer, making and testing over 600 chemicals and identifying three promising candidates within two years.
• 💰 The potential of these strategies could save billions of dollars if applied more broadly across drug discovery programs, improving the efficiency and cost-effectiveness of finding new drugs.

Q & A

What is the main topic of Beatrice Shu's speech?

The main topic of Beatrice Shu's speech is the exploration of chemical space in the context of drug discovery, focusing on improving the efficiency of finding therapeutic compounds.

What is meant by 'chemical space' in the context of drug discovery?

In drug discovery, 'chemical space' refers to the vast number of possible therapeutic compounds that could theoretically be made, limited to commonly found elements and realistic connections.

Why is it challenging to find drugs within the chemical space?

Finding drugs within the chemical space is challenging because only a tiny fraction of chemicals fit well enough to proteins to be useful as drugs, and the exploration of this space requires significant investment and resources.

What is the significance of structure-activity relationships (SAR) in drug discovery?

Structure-activity relationships (SAR) are significant in drug discovery as they relate the structure of a chemical to changes in a protein, which helps in understanding how different compounds interact with biological targets.

What are the two strategies Beatrice Shu's project employs to improve chemical space exploration?

The two strategies are: 1) Designing large libraries of structurally diverse chemicals and making them in small volumes, and 2) Testing these libraries without purifying them using a technique called off-rate screening.

How does the off-rate screening technique work in identifying promising drug leads?

Off-rate screening works by measuring how quickly a chemical dissociates from a protein. Chemicals that fit well to proteins have a slower off-rate, indicating a stronger interaction, which is desirable for drug candidates.

What is the goal of Beatrice Shu's project in terms of improving drug discovery efficiency?

The goal of Beatrice Shu's project is to make the process of drug discovery more efficient by reducing the time and resources needed to explore chemical space and identify promising drug candidates.

How many chemicals has Beatrice Shu made and tested in her project against breast cancer?

Beatrice Shu has made and tested over 600 chemicals in her project against breast cancer.

What are the potential benefits of applying these strategies to more drug discovery programs?

Applying these strategies to more drug discovery programs could potentially save billions of dollars and increase the chances of finding effective drugs.

What is the current state of drug discovery according to the speaker?

According to the speaker, the current state of drug discovery is challenging, with low odds of finding a successful drug, but the speaker is optimistic about improving these odds through innovative strategies.

What is the metaphor used by Beatrice Shu to describe the difficulty of finding a drug in chemical space?

Beatrice Shu uses the metaphor of the Kessel run from Star Wars to describe the difficulty of finding a drug in chemical space, likening it to making the Kessel run in under 12 parsecs.

Outlines

00:00

🧪 Chemical Space Exploration in Drug Discovery

Beatrice Shu from the Faculty of Pharmacy and Pharmaceutical Sciences introduces her project on improving drug discovery through efficient exploration of chemical space. She likens the vast number of potential therapeutic compounds to the stars in the sky, emphasizing the enormity of the task. The concept of chemical space, which is the range of possible chemical compounds, is explained, and the challenge of finding drugs that fit well with disease-causing proteins is highlighted. The speaker outlines the high costs and uncertain outcomes of drug discovery efforts, and introduces her project's aim to enhance the chances of discovering effective drugs by mapping chemical space more efficiently.

Keywords

💡Chemical Space

Chemical space refers to the vast array of all possible chemical compounds that can be made with a given set of elements and their connections. In the context of the video, it represents the extensive area that needs to be explored in drug discovery to find therapeutic compounds that can effectively bind to proteins associated with diseases. The script mentions '60 combinations' as an example of the complexity of this space, emphasizing the challenge of identifying useful drugs.

💡Drug Discovery

Drug discovery is the process of identifying new drug candidates for therapeutic use. It is central to the video's theme, as the speaker discusses the challenges and costs associated with finding new drugs within the expansive chemical space. The video illustrates the high financial investment and the low success rate in drug discovery, comparing the odds to the fictional Kessel Run from Star Wars.

💡Structure Activity Relationships (SAR)

SAR in the video refers to the relationship between the chemical structure of a compound and its biological activity, specifically how it interacts with proteins. These relationships are crucial in guiding the design of new drugs, as they help predict how changes in a compound's structure will affect its therapeutic potential. The script mentions SAR as 'maps' that guide the exploration of chemical space.

💡Protein Binding

Protein binding is a key aspect of drug action where a drug molecule attaches to a specific protein, often involved in disease processes. The video emphasizes that only a tiny fraction of chemicals in chemical space have the right fit to bind effectively to proteins, which is essential for their potential as drugs. The concept is used to highlight the selectivity required for a chemical to be considered a viable drug candidate.

💡Material Synthesis

Material synthesis in the context of the video refers to the creation of large libraries of structurally diverse chemicals. The speaker mentions synthesizing these using material that could fit in the volume of a tablespoon, indicating a highly efficient and compact method for exploring chemical space. This approach is part of the strategies to improve the odds of drug discovery.

💡Chemical Diversity

Chemical diversity is the variety of chemical structures within a library of compounds. The video script discusses using chemical diversity as a strategy to explore large areas of chemical space, which increases the chances of finding compounds that can effectively bind to target proteins. It is a key concept in the speaker's approach to drug discovery.

💡Off-Rate Screening

Off-rate screening is a technique mentioned in the video for testing chemical libraries without the need for purification. It is based on the principle that compounds that bind well to proteins have a slower off-rate, meaning they stay bound longer. The script uses this concept to illustrate a method for rapidly identifying promising drug leads by measuring how long a compound remains bound to a protein.

💡Breast Cancer

Breast cancer is a type of cancer that the speaker is specifically targeting in their drug discovery efforts. The video script details how the strategies discussed have been applied to make and test over 600 chemicals in the fight against breast cancer, highlighting the practical application of the concepts presented.

💡Drug Leads

Drug leads are compounds that show potential as a starting point for the development of a drug. In the video, the speaker talks about identifying promising drug leads through off-rate screening, which is a crucial step in the drug discovery process. The script uses this term to illustrate the goal of their research strategies.

💡Cost Efficiency

Cost efficiency in the video refers to the potential savings in the billions of dollars that could be achieved by applying the discussed strategies to drug discovery programs. The speaker argues that by improving the efficiency of exploring chemical space, significant financial resources could be saved, which is a key message of the video.

💡Kessel Run

The Kessel Run is a reference to a fictional hyperspace route in the Star Wars universe, known for being difficult to navigate. In the video, it is used metaphorically to describe the challenge of drug discovery, likening the odds of finding a new drug to the difficult and risky Kessel Run, emphasizing the difficulty of the task at hand.

Highlights

Speaker Beatrice Shu from the Faculty of Pharmacy and Pharmaceutical Sciences presents her project on improving drug discovery odds through efficient chemical space exploration.

The concept of 'chemical space' is introduced, representing the vast number of possible therapeutic compounds.

Only a small fraction of chemicals in chemical space fit well enough to proteins to be useful as drugs.

The high cost of drug discovery efforts, often yielding uncertain results, is highlighted.

The project aims to enhance the efficiency of navigating chemical space, likening it to making the Kessel run in under 12 parsecs.

Structure-activity relationships (SAR) are described as essential maps in the journey through chemical space.

SAR maps are costly to create, requiring the production and testing of numerous chemicals with purification being a bottleneck.

The first strategy involves designing large, structurally diverse chemical libraries that can be made in small volumes.

The second strategy allows for testing these chemical libraries without purification using off-rate screening.

Chemicals with a slower off-rate, indicating a better fit to proteins, can be identified as promising drug leads without purification.

Beatrice has applied these strategies to fight against breast cancer, making and testing over 600 chemicals in two years.

Three promising drug candidates have been identified through the project's innovative approach.

The potential to apply these strategies to more drug discovery programs could save billions of dollars.

The current statistics of drug discovery are challenged, with the project aiming to improve the odds of finding effective drugs.

The project's innovative methods and theoretical contributions are poised to have a significant impact on the field of drug discovery.

The practical application of the project's findings could lead to more efficient and cost-effective drug development.

Transcripts

[Music]

from the Faculty of Pharmacy and

Pharmaceutical Sciences is Beatrice Shu

and if there was ever someone who we

should have allowed to wear a costume

for their speech it is now because she

is looking at SAR Wars

a journey through chemical space how

many Thai fighters can we see up there

seven eight maybe how about stars

probably many more right well now let's

try and imagine all the possible

therapeutic compounds we could make say

we limit these to commonly found

elements in their realistic connections

that still tend to the 60 combinations

this is called chemical space and in

drug discovery that's a lot of space to

explore to be a drug a chemical must fit

well to a protein key to disease now in

the vast expanse of chemical space only

a tiny fraction of chemicals fit well

enough to proteins to be useful to us as

drugs which means billions of dollars

per year funneled into drug discovery

efforts which may or may not actually

yield a drug so with the odds of finding

a drug lower than Luc destroying the

Death Star you might be thinking I've

got a bad feeling about this and blame

you so my project aims at improving

these odds through efficient chemical

space exploration if drug discovery is

the Kessel run I want to make it in

under 12 parsecs now every journey needs

a map and in our journey through

chemical space these maps are called

structure activity relationships or SAR

and they relate the structure of a

chemical to changes in a protein but the

SAR Maps don't come cheap charting them

requires making and testing large

numbers of chemicals with purification

being the slowest step so we've come up

with two strategies to help fight in

these SAR wars the first involves

designing large libraries of

structurally diverse chemicals and

making them using material that would

fit in the volume of a tablespoon we can

explore huge areas of chemical space

using struck at were using chemical

diversity the second strategy allows us

to test these libraries without

purifying them we've learned that the

slower chemical leaves a pro

Jean measured by its off rate the better

it fits to that protein which makes

sense if you like something you're going

to stay around it much longer

now only chemicals that fit well to

proteins will have that slow off rate

impurities won't which means we can test

these large structurally diverse

libraries of chemicals without purifying

them using a technique called off rate

screening to rapidly identify the most

promising drug leads I've been using

these strategies to help fight against

breast cancer in just two years I've

been able to make and test over 600

chemicals build meaningful

structure-activity relationships and

have three promising candidates but the

sky is the limit if we can apply these

strategies to more drug discovery

programs who knows how many billions of

dollars we could save so so the current

statistics of drug discovery I say never

tell me the odds because we're punching

it in our journey through chemical space

[Music]