Back in the '90's there was an article in Science about a drug addressing HTLV/HTV that then for the first time allowed T4 cells to repopulate. A few years later that drug with spelling slightly changed appeared in the PDR.
Yesterday I ran to a medical research hospital and got a copy of the journal article Inhibition of a viral enzyme by a small-molecule dimer disruptor [Epub ahead of print], an article in Nature Chemical Biology.
This article describes a factor they call DD2, a dimer disruptor, that binds to a viral monomer and traps the monomer in a state such that dimerization is blocked. The region is highly conserved across herpes virus that cause Kaposi's sarcoma, cytomegalovirus, herpes simplex virus, varicella zoster virus, and Epstine-Barr virus. Additionally, there's a low probability that resistance can develop naturally.
It seems to me the drug company developing this will have hit the jackpot while the pharmaceutical industry in general will take a hit with lower profitability projections for drugs addressing pain and cancer.
So, I would like to follow the development of this DD2 through its development to FDA approval and the marketplace. I'd hate to see a pharmaceutical pay a bundle for the right to let it die on the vine. How do I do this?
Bill Johnston
From Journal article to drug?
Moderators: Site Moderators, FAHC Science Team
Re: From Journal article to drug?
The link won't last for long, but here it is:
http://www.nature.com/nchembio/journal/ ... index.html
scroll down and you can get a look at the abstract for free.
That's really an interesting concept! I hope they do make a drug out of it.
OK, now how to track it:
- Run a search every month or so for "dimer disruptor" and see what's new
- Figure out who the main authors are in the paper, and look them up in the scientific databases. See what else they have going on. At the very least, you'll find new search terms.
- Try the NIH research database, "CRISP" , at http://crisp.cit.nih.gov/ . Search there for "dimer disruptor" and the main authors of the paper. I did and found this abstract of Craik's research project.
- Search World Patent Alert for names of the principal authors. See if they've patented any small molecules yet.
This concept would indeed make a great basis for drug design - but before getting too excited I'd recommend looking for background material on dimeric proteases in general. If only viruses have them, great -- but if some important human cellular proteases, or proteases of our symbiotic bacteria, are also dimers, then caution is in order. Also, when is the protease expressed? Is it at a time in the viral infection cycle when disrupting it will do some good? As you read more you will come to understand the fine points and drawbacks of this potential technology.
Hope that helps.
http://www.nature.com/nchembio/journal/ ... index.html
scroll down and you can get a look at the abstract for free.
That's really an interesting concept! I hope they do make a drug out of it.
OK, now how to track it:
- Run a search every month or so for "dimer disruptor" and see what's new
- Figure out who the main authors are in the paper, and look them up in the scientific databases. See what else they have going on. At the very least, you'll find new search terms.
- Try the NIH research database, "CRISP" , at http://crisp.cit.nih.gov/ . Search there for "dimer disruptor" and the main authors of the paper. I did and found this abstract of Craik's research project.
- Search World Patent Alert for names of the principal authors. See if they've patented any small molecules yet.
This concept would indeed make a great basis for drug design - but before getting too excited I'd recommend looking for background material on dimeric proteases in general. If only viruses have them, great -- but if some important human cellular proteases, or proteases of our symbiotic bacteria, are also dimers, then caution is in order. Also, when is the protease expressed? Is it at a time in the viral infection cycle when disrupting it will do some good? As you read more you will come to understand the fine points and drawbacks of this potential technology.
Hope that helps.
-
BillJohnston
- Posts: 2
- Joined: Wed Feb 11, 2009 1:47 am
Re: From Journal article to drug?
Okay, so those who are to hold the patent will be wined and dined and entertain offers. Or, is there an established forum for the bidding? I suppose if the right to use the dimer disruptor were offered on Ebay, a company sponsored by China would bid and win. Or, perhaps a license to develop would be sold to more than a single corporation?
Will the authors of the 50 articles referenced in footnotes be getting anything besides recognition?
Curiosity.
Will the authors of the 50 articles referenced in footnotes be getting anything besides recognition?
Curiosity.
Re: From Journal article to drug?
I don't think you will find a solution to the entire biomedical research/patent/drug industry/insurance industry/for profit medicine situation here.
If you do, please contact the President. I hear he is looking at ways to reduce costs.
If you do, please contact the President. I hear he is looking at ways to reduce costs.
Transparency and Accountability, the necessary foundation of any great endeavor!
-
Kim Branson
- Pande Group Member
- Posts: 3
- Joined: Sat Dec 01, 2007 8:47 pm
- Location: Stanford
Re: From Journal article to drug?
I'm curious as to why you think any pharmaceutical company will 'let this rot on the vine'. They do exist to generate novel therapeutics and sell them.
The pande lab has a long standing interest in small molecule inhibitors of protein-protein interaction.
There is a large difference in the discovery and limited validation of a small molecule and a drug. A drug will need to be potent (i.e nanomolar activity, ) selective (doesn't inhibit anything that causes a side effect, like herg) , bioavaible (gets where we need it to be) and have a appropriate half life (think 1 pill a day vs every 6 hours). Also the final candidate will need to be made cheaply and show actual efficacy in a clinical trial.
It takes a long time to develop a candidate with all these properties, mostly because we don't know enough about all the metabolic systems in the human and the need to run long clinical trials. In general this is a long (10 years +) process. And often after the end of it the drug fails to show any efficacy over existing treatments, or at all.
So if you were to follow this expect it to take 15 years. And drug companies don't need to buy the patent. Often you can get a start by finding molecules similar to those described in the patent and engineering from there. As long as they are not covered you can proceed. And a patent only is worth the money you have to fight infringement. So a smaller company might settle for a share of the profits from an infringement etc.
As for resistance, its pretty hard to show that without having the drug extensively used in the patient population for a few years. Any other statements are often good guesses, and typically handwaving.
a good blog to read if you are interested is 'in the pipeline" by Derek Lowe.
-kim
The pande lab has a long standing interest in small molecule inhibitors of protein-protein interaction.
There is a large difference in the discovery and limited validation of a small molecule and a drug. A drug will need to be potent (i.e nanomolar activity, ) selective (doesn't inhibit anything that causes a side effect, like herg) , bioavaible (gets where we need it to be) and have a appropriate half life (think 1 pill a day vs every 6 hours). Also the final candidate will need to be made cheaply and show actual efficacy in a clinical trial.
It takes a long time to develop a candidate with all these properties, mostly because we don't know enough about all the metabolic systems in the human and the need to run long clinical trials. In general this is a long (10 years +) process. And often after the end of it the drug fails to show any efficacy over existing treatments, or at all.
So if you were to follow this expect it to take 15 years. And drug companies don't need to buy the patent. Often you can get a start by finding molecules similar to those described in the patent and engineering from there. As long as they are not covered you can proceed. And a patent only is worth the money you have to fight infringement. So a smaller company might settle for a share of the profits from an infringement etc.
As for resistance, its pretty hard to show that without having the drug extensively used in the patient population for a few years. Any other statements are often good guesses, and typically handwaving.
a good blog to read if you are interested is 'in the pipeline" by Derek Lowe.
-kim