Field of Science

The Ghosts of Molecules Past?

We are finally filing a patent for a compound on which we have been working since May 2005 or so...or rather, on which our collaborators at Imperial College in London have been working on. That is one of the downsides of computational chemistry (or upside actually). You design compounds on your computer that will target some protein implicated in a disease. That process takes perhaps a couple of weeks at the beginning. After which you fling your designer drug in the experimentalists' face. It's them who then have to keep the midnight oil burning for months; first to come up with a decent strategy to synthesize your molecule, and then give it to the biologists, who in turn take a few more months to test it in cell assays. By the time the compound shows activity, the next ice-age very well might have come and gone. Then you work on some more modifications during the interglacial, after which the experimentalists lock themselves up for one more extended round of geological time. Clinical trials and other events are way off into the next evolution of the Universe after the big crunch.
This is not intended as a put down to the experimentalists, but actually an appreciation of the lengths they have to go to in order to get some results. Also, the computational side of things is not always so easy or so quick, but on a relative basis, it can usually be less lengthier than the experimental side, and also less labour-intensive.

But that's why I decided to do computational chemistry; so that I would have to worry only about the thinking and leave the actual doing to everybody else who works at the bench. It would have been the perfect realisation of my indolence. Alas! I found out that even in computational chemistry, I am not spared the tribulations of learning programs, evaluating data, and actually typing on the keyboard, not to mention walking light years across campus to talk shop with the biologists. So much for the ennui for couch rumination.

I am tempted to say that we are filing a patent for a drug but how premature that statement would be is well summed up in this post by a Pfizer chemist:

"Another surprise is when people find out that I've been doing this since 1989 without getting any drug on the market. I think that some folks are just being polite when I tell that that this isn't unusual, thinking to themselves that I must be some kind of hack. But the general public has, as far as I've been able to see, a very exaggerated idea of how quick and easy it is to find a drug. When I say that if I found a wonderful new compound tomorrow that it might be on the market in about 2015, they think I'm delusional. I wish I were."

Another quote I found also applies to us lowly lab dwellers which the general populace could keep in mind:

"When I meet people with no particular scientific background and they find out what I do for a living, it seems that there are several things that they're usually surprised about. For one thing, many people seem to think that doctors discover new drugs. Some of them don't even think about the drug companies or their role - and if they do, they imagine a lot of doctors working there. Actually, as my readers in the industry can confirm, the only time that physicians really get involved is when the drug is headed into the clinic and dosing in humans. There's not an M.D. in sight while we're validating drug targets, screening compounds, and working to fix their selectivity and activity. (And there's that noisy subset that think that all drugs are discovered in NIH-funded academic labs, but we'll leave that one alone for now)."

In any case, the one thing that keeps cropping up an annoying number of times in such endeavors is luck. We were lucky that 4 out of 10 of our molecules showed activity; it could easily have been none. The whole process was exacerbated by the unfortunate death of one of our collaborators. It is revealing to what pernicious extent you must go to to get your hands on a new molecule that may or may not, probably may not, become a new drug.

The new compound is intended for women whose breast cancer is resistant to the standard treatment of Tamoxifen®, and it turns out there is a considerable number of these.
I hope this one does not end up as the ghost of a molecule past.

Obviously I cannot draw the structure of the molecule here, because then I would have to kill this blog to protect the secret.

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