Every now and then I’ll read that drug X was originally created searching for a cure to disease A, but then they find out its a cure for B instead. How do scientists set out to design a chemical that does specific things? And is it just by chance they discover that it helps with, say, erectile dysfunction and market it that way? Especially when the addition of one atom can seemingly vastly change molecule properties.
In: Chemistry
If you’re talking about how they discover a drug might be useful for something else then it’s just trial and error. They run a trial on a new heart medication and a lot of patients report an interesting side effect of having better sex. Someone then realizes that side effect could make them a LOT of money.
As for intentionally designing a drug in modern times, that’s done by computers. Most drugs work like a key going into a lock. Scientists use computers to model the shade of the lock and how hundreds of hypothetical keys will fit into it. Promising candidates then get lab tested and if they continue to look promising you can move to animal testing and then human testing.
A lot of times they are throwing spaghetti against the wall and seeing what sticks.
The way a drug works is that compounds in the drugs bond with or block other things in the body from bonding with cells in your body. For example pain medications work by blocking pain receptors in your brain from bonding with the chemical pain signals coming from your body.
So a company sets out by trying different compounds and seeing how they interact with the body. They usually have a head start, knowing that certain groups of compounds already do X y z. And then from there they just see what combos and potencies work and what side effects they might cause.
They set out to design a drug to treat A, and in the process of experimentation they notice a stronger side effect. Sometimes that side effect is bad, so they try to engineer it out. Other times the side effect is a positive but unintended one, so they try the hone in on what cause the side effect and see if they can enhance it or isolate it for use as a separate treatment.
For example, Viagra was initially developed to be a treatment for heart conditions. During trials, several male patients noted a particularly strong and firm side effect. The rest is history.
Medicine still proceedly largely through trial and error. Obviously we use the scientific method to make the process more rigorous, but it boils down to trying some things, seeing what works, and building on them.
To seek a treatment for a condition, you don’t just randomly start testing things. You’re usually building on some prior knowledge, which may have been acquired by accident, experiment, or tradition. For example, you notice that a native tribe that eats a certain plant doesn’t get cancer, or that a particular mushroom makes people with infections feel better, or whatever. You start testing the substances in those things in your lab, on bacteria, or individual cells. They don’t harm the cells and they weaken bacteria, so maybe you get some lab mice (praise to the lab mouse) and infect them, and treat them. And they all die immediately. Ok, try again with a different substance from the plant or mushroom. This one works on the mice! Let’s try some other animal…oh, that works too! But the monkeys are also getting very sweaty. Let’s tweak the dosage. Now they don’t sweat but still get better. Great. Let’s start a clinical trial. Hm, people get better but their blood pressure also drops. Interesting. Maybe some part of this could be a blood pressure medication. Let’s go back to the mice with a different combination and dosage and see how they do.
And yes, sometimes it’s not a substance from a plant, but maybe you combine existing ones with known or expected functions and test the combination. For example, you combine a substance that fights cancer but also harms your heart with a drug that helps your heart to offset the side effect. Or you combine a toxic drug with a substance that makes it less toxic. And then it turns out that gives you erections.
Science is fun.
so how exactly did that one guy discover Crack?
Look up the concept called “pharmacophore.” Essentially, molecules interact with receptors based on their chemical “shape” — the distribution of charges, the way the individual atoms on the molecules interact with their environments, etc. Researchers can tell a computer that they need this specific “shape” or pharmacophore to interact with a certain receptor, and the computer will come up with a list of molecules that will “fit.” Then the researchers synthesize the molecules and test them. The whole process is called “drug discovery” and it’s quite fascinating.
Additionally, sometimes they will come up with a molecular “shape” that is designed to interact with one receptor in a specific way, but it will end up also interacting with a different receptor, maybe one they weren’t thinking it would. The new molecule would have what they call “off-target effects” but sometimes those other effects turn out to be more useful than the original effects they were after, or useful for a different thing. They’ll then take that molecule and tweak it more to make it have more effect at the “off” target, or possibly to have less activity at the original target.
Most drugs are organic compounds, so the process is mostly “Well this chemical would be a similar shape to that chemical which we already know works on X, so let’s see if we can synthesise it.”
And if they can synthesize it, they trial it at various stages like agar dishes, animal testing. If it shows promising results, human trials.
When you hear about a medicine being used to treat something different from intended, it’s usually the result of long-term meta studies of patients using the drug for its intended purpose and incidentally reporting changes to other conditions.
These meta studies might find a serendipitous second use for the initial drug, at which point controlled studies are performed targeting this other condition.
The current top answer here said: “The way a drug works is that compounds in the drugs bond with or block other things in the body from bonding with cells in your body.” That’s true.
But the way things bond with one another is based on their physical shape, the physical arrangement of their atoms, as well the electrical charges on the surface of those shapes.
So we can design drugs deliberately by taking what we know about their shapes, and comparing it to the shapes of important biochemicals in our bodies.
So let’s say you want to design a drug that blocks covid from binding to the ACE2 receptor, so that we can prevent it covid from ever getting inside of our cells.
* First you need to know the shape of the receptor. For covid, we know that the receptor is called ACE2. We do already know its shape.
* Then you need to know how covid binds to ACE2. You need to know which locations on the surface of the receptor are important for covid binding. (I’m pretty sure we know that.)
* And then comes the hard step: figuring out what molecule has the right shape, as well as the right electrical charge, to bind to ACE2 in a way that prevents covid from binding.
* There is a certain amount of guesswork involved here, but it’s not all guesswork. You can do a lot of computer simulations of molecule shapes to figure out that they have very low odds of binding to ACE2. This helps you focus on experimental tests that are more likely to work.
* And you can also do your initial steps using proteins instead of living systems. You can check whether your drug candidate binds to the protein at all, and if it doesn’t, well, then it probably won’t in our bodies either.
And even if you do figure out a drug candidate, there’s ***lots*** of other steps that come after. You have to figure out a way to deliver this molecule to the cell; it’s not helpful to take a pill if the drug stays in your stomach and doesn’t get to your cells. The molecule needs to bind specifically: the shape has to bind to ACE2, but not bind to everything else (otherwise it’d have off-target effects). If the molecule binds to ACE2, it shouldn’t disrupt its normal functions.
But that’s how drug design is done using rational planning. It’s not all guesswork, it’s looking at the ability to chemically bind to one another, based on the shapes of the molecules.
For the example of viagra they knew that blocking a protein called PDE -5 would dialate blood vessels. Great said Pfizer! We will work on drugs to block PDE-5.
So they made one and tested it on animals. They seemed to respond well, and didn’t have any negative side effects.
So they gave it to people and it was… okay. It didn’t seem to work very well for agina. But they did notice something weird – male patients would lie on their stomachs. A nurse pointed out they were embarrassed about erections.
Pfizer scientists realised the drug was actually blocking the PDE-5…just it was doing it in the penis, not the heart.
And that is a good example of how these other outcomes happen. The human body uses many different signalling hormones and a huge amount of our medicine is about blocking them or encouraging them.
And cleverly the body uses the same molecule for multiple things.
So for example, dopamine controls both reward pathways and motor control. Which means if you are trying to invent a Parkinson’s drug to help with motor control, you might accidentally invent something that helps with ADHD. Possibly. Its far far far more complicated than that of course in reality.
I work in pharmaceutical research. The first step in drug development is identifying a specific molecular mechanism that plays a key role in a disease. There are tons of academic research papers being published monthly where potential links between these mechanisms and diseases are identified. Often, animal research models are used. These are specifically genetically modified organisms to test if changes to these key “molecular mechanisms” do indeed effect a specific disease. Next a class of molecules (ie potential drugs) are identified which will act on this “key molecular mechanism”. Lots of different variations of these potential drugs are tested in animal models to see which has the greatest effect modulating the expression of this “key molecular mechanism”. It is often here that the first signs of “secondary drug effects” can be first seen. A made up example might be: A drug administered in mice might not shrink their tumors but it’s observed that it makes them lose weight.
Theres honestly a ton more that goes into it, but that’s a small example of how a drug is developed and also how new potential uses for it are identified
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