Drug Discovery: High through-put screening
VX-770 was discovered through a process called high throughput screening, which is a technology powered with robots and supercomputers to scan a huge number of compounds very quickly. They look for molecules that perform specific actions (like opening the gate for chloride ions in the example of VX-770) Before high throughput screening, researchers might be able to screen, let's say 100 compounds a year with old school techniques. I'll go back to the burned out light bulb analogy I used before. If you had to check every light bulb on the planet to discover a single burned out bulb, you would never find it in your lifetime...or in a million lifetimes. High throughput screening changed the face of medical research. It enables millions of compounds to be screened, in a relatively short amount of time. Now, instead of going one light bulb at a time, they can check entire cities or even States at once. It improves your chances exponentially. Researchers will typically get their hands on a collection of compounds that someone sort of "owns." Nearly all of the compounds being screened have never been used for any type of therapeutic purpose. Remember, we are talking about millions or billions of potential compounds. If a molecule is found that makes a little blip on their graph, they isolate it and take it to the lab. This is where they tweak it chemically to see if they can turn that little blip into a big blip(bigger positive effect). Then they can start testing it in the lab on epithelial cells to see how it affects the function of things like the cilia (those little hair like projections that sweep particles like bacteria off the surface of the cell.) After lots of tweaking, the clinical trials process begins. This is exactly what they did with VX-770.
One thing that blew me away at the Conference was how many other correctors already exist and are being tested. We aren't just talking about the Vertex compounds here. They have already discovered many (probably tens or hundreds) of compounds that make those initial small blips. In some of the talks, I would see a slide present 10 correctors I had never ever heard of and how they are working(or not) to fix those two F808 misfolding problems I mentioned in an earlier blog. They are also in the process of screening already existing drugs to see how they act on mutations. They have found some compounds that exibit corrector action for F508. This is directly from something presented at the conference: