What is the drug discovery process?

During my undergraduate degree, people would often ask what course I was studying. Usually the response to “Chemistry with Drug Discovery” was “Chemistry with what?”. No, it doesn’t involve hunting around with a magnifying glass looking for paracetamol. The drug discovery process is a huge chain of events involving numerous people that gets a medicine from initial idea to market. This process can take up to 20 years and many projects fail at various points of the journey. Below is a diagram that I will talk through to take you through the drug discovery process (the blue portion).

Drug Discovery and Drug Testing Processes. Image reproduced from http://nmtpharma.com/en/drug-development-stages/
  1. Identify target – Scientists (mainly biologists) work out how they might target a disease. We have many tiny molecular machines in our bodies called proteins which do various jobs and keep us alive. Sometimes those proteins are missing or go rogue and that often causes a disease, so it becomes the drug target.
  2. Identify compounds – Often, the way to treat a disease is to shut down the protein that is causing the symptoms. These are called inhibitor molecules and they do so by binding to the protein, rendering it useless. Think of it like putting a key in a lock that means a door can’t be unlocked from the other side. These compounds can be found using a number of techniques: by doing a screen (chucking hundreds to millions of potential molecules at the desired protein to see what sticks), working on an existing molecule someone else has identified, or using educated guesses based on the shape of the protein. Chemists will then make dozens, if not hundreds, of these molecules and also slight variants of them based on the same general shape to find a brand new drug.
  3. Establish activity – It’s now back to team biology who test the drug compounds the chemists have made to see if they have the desired effect. This is done using a test called an assay where the individual proteins/cells are monitored to see if adding the drug stops the protein from doing its job. The results of these assays can be relayed back to the chemists who can then make more molecules to ask further questions about how the protein is inhibited and improve on their compounds. Many rounds of this exchange can take place (which is what my PhD project largely involves).
  4. Select clinical candidates – Once scientists are concretely sure about how their drug binds to the protein and have found compounds that shut down the protein with high potency (that is, requiring very little drug to carry out this effect), a shortlist of clinical candidate compounds are selected and made ready for testing in live subjects instead of cells.
  5. Test safety – This is the most controversial aspect of the drug discovery process. Before clinical trials, where drugs are tested in increasingly larger groups of humans, they are first tested in other animal models to see what effect the drug has on an entire organism’s system. Such models include rat, mice, dog and primates, with increasing similarity to human anatomy. I am not involved with this work as a chemist but from what I’ve learned such testing is heavily regulated and I personally think it is a vital step before putting drug candidates into humans. I may discuss this further in a future post.

In the rare occurrence that a drug compound makes it through all of the above stages, it is ready to test in humans. This first part of the process can take years. As I said above, my PhD comes in at stages 2/3 of this diagram and that is 3-4 years worth of work on my part in addition to the work done before me by biologists in identifying the protein I am targeting for treating cancer.

As you can see, the drug discovery process is a rigorous and lengthy one. In a future post I will talk about the various phases of clinical trials that take place to make sure a drug is safe before going on the market.

Are there aspects of the drug discovery process that surprise you? Is this how you expected new drugs to come about? Let me know in the comments.


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