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
As per the comments to the last post, this book, Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization, looks like a very nice overview of these issues for the practicing medicinal chemist. From what I've seen of it, there's a lot of you-need-to-know-this information for people getting up to speed, and it also looks to have collected a lot of more advanced topics into one convenient place. If this is your thing, give it a look.
2. HelicalZz on February 11, 2009 10:22 AM writes...
Thanks Derek,
As I mentioned, I just ordered this and am looking forward to it. A few years back I transitioned from the 'toolmaker' side of biotech to drug development. Being in a small, near virtual company, the traditional and more desirable in my opinion 'experience of others' route was of limited availability. Book learning has helped me not look quite so naive when interacting with more experienced individuals when those opportunities do present themselves.
I'd be curious what other books industry waifs have found useful.
3. retread on February 11, 2009 10:24 AM writes...
Basically drug development, as currently practiced, seems to involve designing (and synthesizing) small molecules to throw at proteins (altering protein function in some way). There has been lots of chemistry developed on the interaction of proteins with polynucleotides (DNA, RNA), but essentially none on the design and synthesis of small molecules to interact with polynucleotides.
Why bother? Well nature has been there and done that with riboswitches, RNAs which can pick out just one small molecule (thiamine or B12 for example) in the complicated chemical soup found in the cell. It should be possible to design and synthesize small organic molecules which will interact and alter the function another class of RNA, namely the microRNAs (which may be the cellular analogue of the bacterial operon). Humans have over 400 microRNAs , with more discovered all the time, and they alter the levels of nearly all the proteins we express.
For further details along this line, see the Chemiotics post of 9 Feb '09 "The further uses of redundancy" on the "Skeptical Chymist" by yours truly. When you look at the site, only a small part of it appears on the part of the site containing all the posts, so at the bottom of the post please click on the "Chemiotics: The further uses of redundancy" (which should really say "continued") to see the rest, which contains the meat of the article.
If these ideas are correct, tons of new chemistry should be involved. Think about it -- a priori, would you imagine that a thiazole hooked to a pyrmidine (thiamine), or a tetrapyrrole (B12) would cause a major conformational shift in RNA. So if correct, the concept would mean much work for the medicinal chemists, currently under seige by megamergers run by lawyers etc., etc. I hate the term paradigm, but it really would be a new paradigm for drug development.
In addition, as Wavefunction said in response to a question about the use of force fields to model interactions with polynucleotides, in his post of 24 Jan '09 on the Curious Wavefunction "I would be strongly critical about using classical force fields to model the highly charged and ionic nucleic acids because of the well-known force field inadequacies in modeling electrostatic interactions that I have mentioned in previous posts"
So the idea, if correct, should be great grist for the computational chemistry mill as well.
"In the Pipeline" gets tons of comments, which is at least 50% of what makes it so good. "The Skeptical Chemist", while a great venue, gets very few on all the posts. If you read what I wrote and agree/disagree please leave your thoughts there.
That is definetely a very useful book for medicinal chemists and I also read very recently 'Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research ' (http://www.amazon.com/Real-World-Drug-Discovery-Pharmaceutical/dp/0080466176). This one is well written and should be recommended to every on-boarding medicinal chemist.
College chemistry, 1983
The 2002 Model
After 10 years of blogging. . .
, looks like a very nice overview of these issues for the practicing medicinal chemist. From what I've seen of it, there's a lot of you-need-to-know-this information for people getting up to speed, and it also looks to have collected a lot of more advanced topics into one convenient place. If this is your thing, give it a look.
1. Wavefunction on February 11, 2009 9:32 AM writes...
It's a great book. Just bought it a month or two ago and now actively using it for our project.
Permalink to Comment2. HelicalZz on February 11, 2009 10:22 AM writes...
Thanks Derek,
As I mentioned, I just ordered this and am looking forward to it. A few years back I transitioned from the 'toolmaker' side of biotech to drug development. Being in a small, near virtual company, the traditional and more desirable in my opinion 'experience of others' route was of limited availability. Book learning has helped me not look quite so naive when interacting with more experienced individuals when those opportunities do present themselves.
I'd be curious what other books industry waifs have found useful.
Zz
Permalink to Comment3. retread on February 11, 2009 10:24 AM writes...
Basically drug development, as currently practiced, seems to involve designing (and synthesizing) small molecules to throw at proteins (altering protein function in some way). There has been lots of chemistry developed on the interaction of proteins with polynucleotides (DNA, RNA), but essentially none on the design and synthesis of small molecules to interact with polynucleotides.
Why bother? Well nature has been there and done that with riboswitches, RNAs which can pick out just one small molecule (thiamine or B12 for example) in the complicated chemical soup found in the cell. It should be possible to design and synthesize small organic molecules which will interact and alter the function another class of RNA, namely the microRNAs (which may be the cellular analogue of the bacterial operon). Humans have over 400 microRNAs , with more discovered all the time, and they alter the levels of nearly all the proteins we express.
For further details along this line, see the Chemiotics post of 9 Feb '09 "The further uses of redundancy" on the "Skeptical Chymist" by yours truly. When you look at the site, only a small part of it appears on the part of the site containing all the posts, so at the bottom of the post please click on the "Chemiotics: The further uses of redundancy" (which should really say "continued") to see the rest, which contains the meat of the article.
If these ideas are correct, tons of new chemistry should be involved. Think about it -- a priori, would you imagine that a thiazole hooked to a pyrmidine (thiamine), or a tetrapyrrole (B12) would cause a major conformational shift in RNA. So if correct, the concept would mean much work for the medicinal chemists, currently under seige by megamergers run by lawyers etc., etc. I hate the term paradigm, but it really would be a new paradigm for drug development.
In addition, as Wavefunction said in response to a question about the use of force fields to model interactions with polynucleotides, in his post of 24 Jan '09 on the Curious Wavefunction "I would be strongly critical about using classical force fields to model the highly charged and ionic nucleic acids because of the well-known force field inadequacies in modeling electrostatic interactions that I have mentioned in previous posts"
So the idea, if correct, should be great grist for the computational chemistry mill as well.
"In the Pipeline" gets tons of comments, which is at least 50% of what makes it so good. "The Skeptical Chemist", while a great venue, gets very few on all the posts. If you read what I wrote and agree/disagree please leave your thoughts there.
Permalink to Comment4. obsoletechemist on February 12, 2009 10:15 AM writes...
Too bad no one is interested in small molecule drug discovery any more
Permalink to Comment5. G Experiment on February 14, 2009 8:05 PM writes...
If you go to Kerns's ACS short course of the same topic you get this book for free, which is how I got mine.
Permalink to Comment6. Pathi on February 14, 2009 8:34 PM writes...
That is definetely a very useful book for medicinal chemists and I also read very recently 'Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research ' (http://www.amazon.com/Real-World-Drug-Discovery-Pharmaceutical/dp/0080466176). This one is well written and should be recommended to every on-boarding medicinal chemist.
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