There are some perqs to being a consultant. I go to work most days in my jammies, I can work from anywhere with WiFi, and get to work with great people. I also have a lot of freedom with what I can say/do/write. Back in April at the CHI Drug Discovery Chemistry meeting, I ran into an editor from an ACS publication. Now, if you have ever been at a conference with me you know I am a social butterfly. New face, let's chit chat. This editor was very nice and after some social niceties, I asked who is refereeing your journal? This was a general query having to do with some poor quality fragment papers recently, and before I even saw this! She was polite and asked what do you mean? I said, well I blog on fragments and we come across crap in JMedChem and the like all the time. Like this. I think at this point she obviously was thinking of me like this 
. Then I mentioned that the blog was Practical Fragments and her attitude changed. So, this blog has "street cred"!! She then asked me if I would write a Viewpoint on the future of FBDD. Sure, I said. This could be fun.
. Then I mentioned that the blog was Practical Fragments and her attitude changed. So, this blog has "street cred"!! She then asked me if I would write a Viewpoint on the future of FBDD. Sure, I said. This could be fun.
At the same time, I was preparing a talk for the Zing FBDD conference. So, I decided to make that talk (that's a link to SlideShare, I hope it works) a demo for the Viewpoint. Give it a read, its short and sweet (at least I think).
For those of you without 10 minutes to spare, here are the take home points from the Viewpoint:
- Fragonomics is a key component of most (all?) hit generation processes
- It is a fully mature field. The current debates amount to quibbling about details.
- It has no future as a stand-alone field. But there are still challenges for it to tackle.
- Medchemists no longer rule the field.
"The age of the medchemist is over; now is the time of the biophysicist."
This got some serious push back at the conference, and I expect (hope?) it will here too. Of course, I am paraphrasing this. I am not suggesting that medchemists make like the Elves and sail off to Valinor. They are still incredibly important and can still play a role in early hit generation. However, the focus, thanks to Fragonomics, is vastly different. A chemically trained biophysicist can run a fragment-based hit generation project and you don't have to have engage the most precious resource (medchem) until well into the process. This is a good thing.
Well, I have planted my flag. Now its time for you all to weigh in.
Much as I'd like to visit Valinor, I'd say that medicinal chemists are still just as essential today as they ever have been. Not only are we needed to design libraries and avoid PAINS, it's pretty difficult to transform a millimolar fragment to a lead - let alone a drug - without medicinal chemistry!
ReplyDeleteNot saying they aren't essential. I am saying the need for their engagement has been pushed back in the whole process, thereby easing a resource crunch early in the process and putting them later where they have more impact.
ReplyDeleteDerek comments on it: http://pipeline.corante.com/archives/2014/08/21/fragonomics_eh.php
ReplyDeleteI always think discussion about who is the most important is missing the point. You can be as great a Med Chemist or Biophysicist as you like, but no one single person has the expertise in biology, chemisty, biophysics, assay dev, DMPK, safety etc to be able to unilaterally make decisions on the direction the project takes. I really think our industry has struggled over the past two decades because Medicinal Chemists ruled the roost to the detriment of other equally skilled scientists in other fields. I think it would be equally foolish for biophysicists to assume they can replace medicinal chemists in this role.
ReplyDeleteFor me the key to successful drug discovery is team work, humility and knowing where the limits of your knowledge are.
More and more, particularly in PPI targets, I am seeing project teams come forward with molecules that bind avidly to the target protein. The biophysicists and CADD guys (and gals) are justifiably proud of their contributions,
ReplyDeleteUnfortunately, too often, these molecules do nothing functionally, and thus are essentially useless as starting points for a drug discovery project. A (decent, or at least trained by me) medicinal chemist would have asked that question up front.
So, there is still education to be imparted, on both ends. As noted above, "most important" misses the point.
@Anonymous, why would you expect a weakly binding compound to necessarily have a functional effect?
ReplyDeleteTeddy -- I said "avidly". I have seen teams (internal and at potential "partners") optimize "potency" without regard to functional effects.
ReplyDeleteDelivering a potent ligand of absolutely no use to me.
I really don't care who makes the molecules, or who drives the project. Someone needs to keep their eye on the ball.
(I vehemently disagree with the comment above that "no single person has the expertise . . . to unilaterally make decisions on the direction the project takes" BTW. I know several such people. Rare, true, but not unknown.)