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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Munos On Big Companies and Small Ones | Main | The Cost of New Drugs »

December 11, 2009

Another Take on the Munos Paper

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Posted by Derek

Eric Milgram over at PharmaConduct has an excellent post up on the same paper I've been discussing this morning. As another guy who's been around the block a few times in this industry, he's struck by many of the same points I am (to the point of also linking to Wikepedia's page on Poisson distributions!)

And he has some interesting data of his own to present, too - well worth checking out.

Comments (11) + TrackBacks (0) | Category: Business and Markets | Drug Development | Drug Industry History


COMMENTS

1. Anon on December 11, 2009 4:56 PM writes...

Remember the smackdown on the diazaannulenes? http://pipeline.corante.com/archives/2007/11/29/neat_wish_it_were_true.php

Christl brings it again!
http://dx.doi.org/10.1002/anie.200901741

Permalink to Comment

2. Jeffrey Soreff on December 12, 2009 9:47 PM writes...

I have a really dumb question. Has anyone tried looking for new drug leads by looking for binding at _all_ of the proteins coded for in the human genome, regardless of whether their function is known? With 23,000 genes, it seems like there should be the potential for a comparable number of useful drugs (ok, binding to structural proteins might not do anything useful...). Has anyone tried anything like that?

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3. weirdo on December 12, 2009 10:19 PM writes...

You would need binding assays for all of them. To justify the expense of doing so, you'd need a reason or two. Even with reasons, academia and biotech and big pharma all put together have a pretty lousy track record of turning molecules that bind particular proteins selectively into actual drugs -- or even tools that give unambiguous answers.

But the short answer to your question is "yes". It's called "systems biology" and "phenotypic screening".

Permalink to Comment

4. Jeffrey Soreff on December 12, 2009 10:50 PM writes...

Many thanks!

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5. Mutatis Mutandis on December 13, 2009 7:34 AM writes...

I don't think it makes much sense to target "all" of them, but I've heard people discuss the idea of identifying the central proteins and interactions in the signalling networks through systems biology, and then systematically discovering molecules to target all of those.

They would of course be useful tool compounds to explore systems biology further. But you could also put them on the shelf with the confidence that sooner or later nearly all these critical interactions will be found to be relevant to a pathology of some kind.

It seems unlikely that people will try to do this through binding assays, I would bet more on phenotypical studies (HCS and microarrays) aiming to find drugs that mimic phenotypes established by RNAi. However, I'd like that to be done on primary cells or at least stem-cell derived cells.

Permalink to Comment

6. petros on December 13, 2009 8:42 AM writes...

Having heard a couple of talks on the targets issue, at a Chemical Biology meeting last week, the suggestion seems to be that there are about 3000 viable drug targets encoded by those 23000 odd genes, not all of which are likley to be tractable small molecule targets

Permalink to Comment

7. fromsgc on December 14, 2009 5:17 AM writes...

I never figured out where this number, 3000 came from. It certainly implies the good and thorough understanding of human physiology which I realy doubt. IMHO it is some rubbish guess from some rubbish Nature Reviews Something.

Permalink to Comment

8. petros on December 14, 2009 6:10 AM writes...

The druggable genome was calculated by Hopkins & Groom in a collaboration between Pfizer and Inpharmatica

see http://www.oecd.org/dataoecd/35/0/35641354.pdf

But it was a Nature Rev Drug Discovery paper

Permalink to Comment

9. fromsgc on December 14, 2009 6:38 AM writes...

Thanks for the link !

So 3000 is the estimate of the number of proteins which potentially can be targeted by small molecules based on current chemistry/screnning technologies.
Not the number of proteins related to desease phenotypes...

Permalink to Comment

10. Grant Mayeda on March 1, 2012 3:30 PM writes...

Thanks for the various tips shared on this blog. I have seen that many insurers offer shoppers generous savings if they choose to insure many cars together. A significant number of households currently have several vehicles these days, especially those with mature teenage young children still located at home, along with the savings on policies can easily soon increase. So it makes sense to look for a good deal.

Permalink to Comment

11. mulberry uk on July 9, 2012 6:04 AM writes...

Excellent read, I just passed this onto a colleague who was doing some research on that. And he actually bought me lunch since I found it for him smile So let me rephrase that: Thank you for lunch! "Procrastination is the thief of time." by Edward Young.

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